Post an Anime couple that can never happen due to certain circumstances .

Eichi X Mitsuki (Full Moon Wo Sagashite)~

They both loved each other (although Mitsuki realized it a little too late). It never happened because **SPOILER** Eichi died. In the end, Mitsuki never got to tell Eichi how much she loves him. Well, actually Eichi's soul has always been with Mitsuki so technically, he most likely knew about her true feelings.

The (manga) ending made me cry so hard. As Eichi's soul was fading away from Mitsuki, he was reluctant to go but seeing how Mitsuki was already happy as she was living her dream and being beside Takuto (the guy Mitsuki ended up with), he finally let go with tears in his eyes. It was very bittersweet for him~

TT_TT

No matter how much she loves her, Tsukushi can simply not marry her sister Tsukiko in The Hentai Prince and the Stony Cat. She thought that if she moved to Massachusetts, where same sex marriages are legal, and cut off all familial ties with her it would work. But alas, it doesn't work that way. Besides, Tsukiko wants nothing to do with the harebrained idea.

Sayaka and Kyousuke

It's going to be difficult, but I'll try to explain.
Sayaka is in Liebe with Kyosuke, so she sells her soul to Kyuubey in exchange of a wish. Her wish is to heal Kyousuke's arm so he can play violin again. (SPOILER) Kyousuke never gets to know that it was Sayaka who saved him and starts dating Sayaka's friend. After that, Sayaka becomes depressed and dies. Although she could have been saved thanks to Madoka's wish, she prefers to leave things the way they were so Kyousuke can play violin and be happy with the other girl.

Welllll....
This is not technically an Anime couple, but it is a Manga couple and it fits this question!

Riiko and Night from the Manga Absolute Boyfriend.
They are perfect together but can't be together because..well.. Night isn't real, he's an 'action figure' as they call it and is a robot who was shipped over to her house through some sort of dodgy online purchase xD
My plot synopsis sounds terrible right there, but I promise the Manga is very good and addictive hahah.

But yeah. Cried in the final chapters of this Manga tbh, they were so good together, but it was wrong for them to be together :'(

And this isn't really a spoiler since it's incredibly obvious that it would turn out this way right from the beginning :/