This is a very simple process to test.
1) load a new epub into Calibre
2) edit the metadata of that epub within Calibre by changing the cover image
3) right click on the epub from within Calibre and select "open containing folder"
you will see (at least) three files: cover.jpg, metadata.opf, and ___.epub (plus any other formats you may have converted to)
4) open the cover.jpg. It will be the new cover that you just changed.
5) drag the epub to whichever viewer you wish (I used ePubreader in firefox because it was easy)
6) you will see the ORIGINAL cover
7) go back to Calibre and "save to disk"
8) again drag the epub to your favorite viewer...you will see the new cover.
I just did this and...voila!