Nearby resident David Savige said he could smell the fish early Sunday morning before he investigated.
He said there were "heaps" of yellowbelly, redfin and Murray cod near the Echuca Rd and Kalimna Dve sides of the lake.
He said he was "extremely concerned" for the welfare of fish and lake.
“It's pretty awful because it's one of my favourite fishing spots,” he said.
“I've been fishing there for some time, and I'm a catch-and-release fisher to help preserve the lake so it's important we can find out why this is happening.
“I feel bad for the people that live around the lake who have to smell and see the dead fish because it isn't pleasant.”
Mr Savige said earlier in the week there was a case of a Murray cod that was saved from a lack of oxygen by other fisherman.
Mr Savige said he was also concerned by the thickness of weed in Craigmuir Lake.
Another resident said there were reports of a dog falling sick after swimming in the lake and there appeared to be a sludge at the south-east end.
Greater Shepparton City Council says it has contacted the EPA, who is now investigating.