Handler has hosted Chelsea Lately on the network for eight years, but has long been dissatisfied with the relationship, The Hollywood Reporter said.
"Chelsea intends to leave when her contract expires. She hired me to figure out her life after E! We have at least seven suitors and many ideas," Handler's manager, Irving Azoff, said.
A spokesperson for E! declined to comment on the news.
"Chelsea has nine months left on her contract and E! will not comment on the future of Chelsea Lately at this time," said the spokesperson, whose name wasn't reported.