Michael McGimpsey has backed a senior health official's view that up to 4,000 jobs would go in the health service if Stormont's draft budget is approved.
Regional Health and Social Care Board chief executive, John Compton, said waiting times would also be longer.
It was announced on Wednesday the health budget would increase by £326m.
But the health minister agreed with Mr Compton's comment they would be "several million pounds short".
He said his view that up to 4,000 jobs would be lost was a "fairly accurate assessment".
"There will also be issues around the voluntary and community sector," Mr McGimpsey added.
"I have been warning for some time about job losses, about closures and about radical changes for the way we deliver service.
"I am looking at a budget that next year, starting on 1 April, I am £100m short.
"This is the reality and I have a duty to explain that."
Earlier, Mr Compton said he was "pretty confident" that "between 3,000 and 4,000 jobs" would be lost over the period of time covered by the draft budget if it was approved.
"The board will be considering in January a detailed response to the budget that will be much more specific, but clearly we will have to examine where we are providing services right across the Province," he added.
"It is clear that will affect all grades of staff - professional staff, administrative staff, management staff.
"We would try to do that in a sensible way by managing normal turnover of workforce and all of those sorts of issues, but undoubtedly there will be significant job reductions if this budget maintains."
Northern Ireland Finance Minister Sammy Wilson said on Wednesday there were no plans for water charges over the next four years in the budget plan.
He also confirmed in the draft budget that the regional rate, the portion of rates collected by Stormont, would increase by inflation in the same period.
There will be a 15p plastic bag levy while 12,000 civil servants face a two-year pay freeze.
If the draft budget is implemented, education would lose £67m, regional development £63m and justice £48m.