Any hope of the Black Cats following up their crucial win over Reading by ending a barren run at Manchester United that stretches back to 1968 was effectively ended when they fell two goals behind after just 20 minutes.
Although Sunderland showed spirited resistance in the final half hour, Frazier Campbell's header was all O'Neill's men had to show for a 3-1 defeat that leaves them just a point above the drop zone.
It is not a comfortable position to be in - and with Christmas encounters with Manchester City and Tottenham looming, next Saturday's trip to Southampton is taking on 'must-win' proportions.
"It is almost inevitable and pretty natural that when a side is trying to put a bit of form together, confidence is essential," said O'Neill.
"We scored an early goal against Reading on Tuesday and you could see the confidence coming right back to the team.
"But if you concede two goals against anybody, particularly away from home, you will have an uphill struggle.
"Against Manchester United we have made it much easier than we could have done."
O'Neill refused to take the easy option of regarding the Old Trafford visit as a bonus game, even though he accepted few, certainly not Manchester City, would have expected them to get anything.
What they did get was another worry regarding top scorer Steven Fletcher, who suffered a back injury in the warm-up that worsened significantly during the first half and left the Scot unable to come out for the second.
At least his replacement Connor Wickham produced a pleasing performance.
The 19-year-old moved north from Ipswich for £8.1million at the start of last season but has found goals at the highest level difficult to come by.
He has only one to his name and did not add to that tally yesterday. However, Wickham caused a United defence bolstered by the return of skipper Nemanja Vidic some major headaches, which could be handy if Fletcher is ruled out for an extended period.
"Connor did very well," said O'Neill. "There were encouraging signs from him. He was trying to hold it up and bring other people into play."
Wickham was delighted with his contribution too as Sunderland tried to complete an unlikely comeback.
"I always aim to create chances," he told www.safc.co.uk.
"It's just about getting enough people in the box to try and finish them off.
"We know we could have reduced the deficit further - we had chances and could have buried them."