O’Nien has been struggling with a shoulder injury for most of the campaign, and has suffered repeated dislocations.
The midfielder has been in consultation with a surgeon this week, and it has been decided that the 27-year-old can no longer put off dealing with the root of the issue.
He will be out for three months as a minimum, but potentially considerably longer.
Sunderland’s complete lack of full back options saw them switch to a back five for the crucial win over Cambridge Town, with Leon Dajaku playing at wing back.
Johnson admitted he may have to use that shape again going forward.
“He needs to have an operation,” Johnson revealed.
"He’ll be out for three months minimum, anywhere between three and nine depending on how much they have do.
“We might have to register myself and Jamie McAllister! I’m going to have to be tactically flexible, and every now and then we’re going to have a square peg in a round hole.
We probably had fifteen players today.
"We’ll have to go again in this tough spell and bundle through to January.”
Sunderland suffered another injury just moments before the game began, with Corry Evans withdrawing after suffering a thigh injury in the build up to the game.
Lynden Gooch was brought into the side and did well in a relatively unfamiliar right-back role.
Johnson had already named a youthful bench, and ultimately was left with just six substitutes.
Academy product Will Harris was brought in the closing stages, his second league appearance of the campaign.
“He just felt his thigh,” Johnson said.
“Even more reason to give credit to the lads.
“Gooch came in at right wing back and was outstanding, absolutely outstanding.
“We’re going down like flies and it’s tough to take, because we’ve got a lot of tough games
“Having said that, Leon did well out of position and Will Harris came on for us as an academy player, so there were some good moments there for us.”
The 2-1 win lifted Sunderland to fifth in the table.