With an hour gone at Windsor Park on Friday night, O'Neill would have been contemplating a famous World Cup qualifying victory with his side 2-1 up and Portugal having lost Helder Postiga to a red card.
But Chris Brunt and Kyle Lafferty were both dismissed to allow Paulo Bento's side back into the game and Real Madrid superstar Cristiano Ronaldo obliged with a 15-minute hat-trick to seal a 4-2 win.
Brunt and Lafferty will now be absent when their team-mates fly to Luxembourg on Sunday morning and O'Neill has other problems to deal with too.
He confirmed that Derby forward Jamie Ward, who has excelled in his last two appearances and scored his first international goal against Portugal, is a doubt alongside Shane Ferguson.
Both were substituted in the second half in some discomfort, while an Irish Football Association official said that Niall McGinn was also nursing an injury.
With Aaron Hughes, Ryan McGivern and Craig Cathcart already injured before the squad met in Belfast, O'Neill could potentially be down to the bare bones.
"We will have to sit down and assess our options," he admitted.
"As well as the red cards the biggest blow is a couple of injuries.
"Wardy is possibly out and Fergie may not be available, so that will give us something to think about."
Source: PA
Source: PA