The showrunner said that both Ellen Pompeo and Sandra Oh's characters will struggle with the decision to stay at Seattle Grace or move on elsewhere.
Of Meredith, Rhimes explained: "It's going to be interesting for her. Seattle Grace is her home. These people are her family. That's what she spent the past eight years establishing.
"The idea of leaving or staying is going to weigh heavily on her and going to be pretty hard for her to deal with...Derek (Patrick Dempsey) would go with her wherever, and Derek is encouraging her to take the best job there is, wherever that is."
Rhimes went on to discuss how Cristina's possible departure will affect both her mentor Teddy (Kim Raver) and husband Owen (Kevin McKidd).
"It's hard for both of them," she told TV Guide. "Cristina is very gifted and a lot of people are going to want her. For both Teddy and Owen, there's going to be some struggle there in terms of letting go. Or if you can let go or if you should let go.
"Cristina will eventually have to decide what's going to happen in the relationship [with Owen] versus what she wants in her career."
Rhimes confirmed that the Meredith, Cristina relationship will also be addressed in an upcoming episode and insisted that no members of the cast are aware of who is leaving.
Grey's Anatomy airs Thursdays at 9/8c on ABC.
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