Overstock.com's founder and CEO, Patrick M. Byrne, said he will take a personal leave of absence for medical reasons.
Byrne recommended to the board of directors that current general counsel Mitch Edwards take over as acting CEO.
The Salt Lake City-based online retailer is unsure of whether he will return.
The cause for the leave is stage IV hepatitis C. Byrne contracted it in China in 1984 when he had a head wound sewed up under what he termed as "less -than-ideal" conditions.
Hepatitis C is a liver disease caused by a virus that is transmitted through blood. A common mode of infection includes the inadequate sterilization of medical equipment and the transfusion of unscreened blood products.
"I have finished treatment and think I have it beat but only time will tell," Byrne said in a statement.
Overstock.com's shares rose 36 cents, or 2.5 percent, to $14.69 in morning trading. Its shares have fallen more than 40 percent over the past year.