Deadline.com reports Winfrey, who serves as CEO of the network, cited an ineffective "cost structure" as the reason for the decision.
"As CEO, I have a responsibility to chart the course for long-term success for the network. To wholly achieve that long-term success, this was a necessary next step," she said.
As part of the network's restructuring, OWN laid off 20 percent of its staff, including its senior vice president of production, while other executives are shifting into new roles.
On Friday, OWN announced it had cancelled O'Donnell's evening talk show after five months. The final episode of The Rosie Show will air March 30.
OWN has struggled to find a sizable audience since launching in early 2011.