Asymmetrical shape keys on mirrored mesh?

My character has a mirror modifier, followed by an armature modifier: works like a charm, no need to apply the mirror, as symmetrical vertex groups were automatically generated.

Now I created a shape key to close the eyes, and I had wanted to split this into two keys using vertex groups for left and right half of the character, but this doesn’t seem to work? Is there any way to get this to work without applying the mirror modifier?

Not that I know of. Using a mirror mod for modeling and weight painting is great because you can cut your work load in half. When you get to the shapekey stage of character creation, you will want to apply the mirror.

Don’t apply the mirror to the main mesh, make a copy first. Continue working and creating shapekeys on the new copy. You also want to be certain that you are finished with weight painting and any other changes you want to make for the mesh. Adding new faces, edgeloops, etc, will break your shapekeys as you are changing the basis. The basis is the road map for the vertex positions. Shapekeys rely on those positions. You will loose a lot of work if you make model changes after creating your shapekeys.

Also, you cannot apply modifiers to a mesh with shapekeys.

Good luck!

To add to what DanPro said, shapekeys are applied to the mesh/calculated before any modifiers, so in this case they transform the mesh before the effect of the mirror modifier.