I had a problem like this. I was trying to run in windowed mode and when I did I had no mouse. Stardock sent me the following:

Try going to
C:\Users\*yourname*\AppData\Local\Ironclad Games\Sins of a Solar Empire\Setting\user.setting

and set 'VideoIsWindowed FALSE'.

I did that and it fixed it so I could play. For some reason my mouse does not show up when in windowed mode and this allowed me to switch back to full screen mode where my mouse does work.

I hope it works for you too:)

ive had this problem before. try not playing in full screen, this problem has occured to me in several games as i own ovr 100, and normaly that was the solution. this has also happend with sins to me and the solution was the same, for me. I remember this also occured to AoE 3 for me, solution was the same. - Bad Boy