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Grey's Anatomy: 10 Most Heartbreaking Separations | ScreenRant

The sheer number of breakups on Grey's Anatomy's record run is staggering. This Shondaland drama has split couples up at the drop of a hat, but while some relationships ended without much noise, others like the separation of Jackson Avery and April Kepner have had fans reaching for their tissues.

RELATED: 10 Romances Nobody Saw Coming In Grey's Anatomy

Separations are hard, especially when it's a beloved couple like Mark and Lexie or an adorable one like Alex and Jo.  Then there are the polarizing pairings like Teddy and Tom or Meredith and Andrew, but irrespective of whether the couple made sense or not, within the context of their own story, these breakups hurt.

10 Meredith & DeLuca

Meredith's first real relationship after Derek's tragic passing was with Andrew DeLuca. Fans might have been of two minds about their chemistry but there is no doubt that their separation was disheartening.

Meredith had been through terrible challenges in her life already, and fans are always hoping that she finally finds some happiness. Here she was, just starting to dip her feet into the dating pool again, and she actually seemed happy with DeLuca. Alas, he broke up with her in season 16, leaving fans wondering yet again whether Meredith was destined to ever truly be happy.

9 Meredith & Derek

Derek and Meredith might have seemed like the perfect couple, but things soon turned sour when the former was revealed to be married. Addison's arrival at Seattle Grace at the end of season 1 sent Derek and Meredith's relationship spiraling, and there was a phase in season 2 when the pair seemed to be going their separate ways.

The two parted ways yet again in season 4 when Meredith appeared hesitant to commit to the relationship. They continued to go through ups and downs with both of them dating other people. Their separation period was one of great agony for fans as they waited with bated breath for their favorite couple to reunite. Their frustration grew even more, as MerDer ere clearly meant to be together.

8 Link & Amelia

Link and Amelia quickly became an adorable Grey's Anatomy couple after they started hooking up and Amelia became pregnant unexpectedly. The season 17 finale ended with Amelia being unable to accept Link's proposal and the latter seeking refuge with his good friend Jo.

RELATED: 5 Ways Amelia And Link Make Complete Sense In Grey's Anatomy (& 5 Ways They Don't)

Link and Amelia worked because their relationship seemed, to provide Amelia with a tad bit of stability — for once. As someone who had been through tremendous suffering in the past, fans hoped that Amelia would finally catch a break. Yet, it seems like happiness is still going to elude her for a while since in season 17 she was shown questioning her current situation.

7 Owen & Cristina

Cristina's prolonged romance with Owen took her on a roller coaster ride. The two broke up more than once as they kept reconciling at some level. But the final breakup in the season 9 finale was heartbreaking, especially since both had put in a lot of effort to save the relationship.

After helping each other through post-traumatic stress, they eventually split up over the different lives they envisaged for themselves. Seeing them unable to keep their hands off each other but knowing that they couldn't be together was crushing for many a fan.

6 Tom & Teddy

Tom and Teddy were one of the more recent couples to separate. Grey's Anatomy fans may have divided opinions on Tom, but for all his sarcasm, he was genuinely in love with Teddy. He had been through a fair bit of tragedy in his own life, having lost his son to an accident, and it seemed unfair somehow that the one person at Grey Sloan Memorial who saw his softer side didn't ultimately choose him.

In one of the most poignant moments in the Tom-Teddy-Owen triangle, Tom was seen putting together a crib for Teddy's baby while the latter was giving birth with Owen by her side. Teddy finally broke it off with Tom once and for all in season 17.

5 Jo & Alex

In one of the worst separations in Grey's Anatomy history, Alex broke up with Jo in season 16 in a Dear John letter reminiscent of the one Izzie wrote to him years ago.

RELATED: 10 Greatest Betrayals In Grey's Anatomy, Ranked

The breakup was tremendously unfair to Jo, who had been living with depression and needed all the support she could get from her husband. For Alex to leave her then made very little sense for a character that had evolved with leaps and bounds over the years. Furthermore, the separation marked Alex's exit from the show after 16 long years, and that naturally broke fans' hearts.

4 Callie & Arizona

Callie and Arizona were one of the biggest fan-favorite couples on the show. However, like every Shondaland character, these two went through some terrible times, which pushed them away from each other.

Fans felt gutted in season 11 when Callie told Arizona that she had grown to enjoy her time away from her and wanted more of that independence. Their separation might have been a long time coming, ever since the devastating plane crash in season 8. The couple's split meant that they had grown tired of their constant friction and Callie, wanted a life that didn't revolve around Arizona, especially after the latter became one of the worst Grey's Anatomy characters to have cheated on her partner.

3 Izzie & Alex

Grey's Anatomy fans spent years moving on from Alex's breakup from Izzie, as they were a fan-favorite couple who were two of the original interns in the show.

Izzie and Alex on Grey's Anatomy didn't always make sense, but there was an element of charm in how Alex embarked on his path to bettering himself. The two broke up at first over a misunderstanding when Izzie mistakenly thought Alex had canvassed to get her fired, and then finally in season 6 when he let her go.

2 Lexie & Mark

Mark and Lexie had one of those heartrending on-and-off relationships that kept fans perpetually frustrated. The two were made for each other but never got around to putting their feelings above other petty issues during their time at Seattle Grace.

They broke up in season 6 when Mark tried to railroad Lexie into accepting a life where his newfound teenage daughter and her newborn would live with them in the same house. Since then, the couple shared moments when they nearly got back together but never fully did. The older, arrogant Mark was humbled by the younger, gentler Lexie, and fans wished that they would finally figure things out. Of course, that was never to be as Lexie died shockingly in the season 8 finale of Grey's Anatomy, with Mark following suit, thereby rendering their love story and separation even more poignant.

1 Jackson & April

One of the most heartbreaking separations on Grey's Anatomy was that of Jackson and April. The two had sweet chemistry and got together very dramatically when April ran away with Jackson at her own wedding, leaving Matthew high and dry at the altar.

Unfortunately, Jackson and April's romance and marriage were fraught with stress and tragedy: their little son, Samuel, was diagnosed with a rare bone disease that caused his death hours after his birth. The pain was unbearable, and the couple separated in the season 11 finale and eventually divorced.

NEXT: 10 Best Stormy Relationships From Grey's Anatomy, Ranked

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