The West Midlands outfit went into the EFL Cup third round tie at the Amex Stadium having let slip a lead against Newcastle United in the Premier League on Sunday.
That kept Wolves on one point from four top-flight fixtures, despite generally performing well in difficult encounters against Arsenal, Chelsea, Nottingham Forest and the Magpies.
Despite naming a much-changed side, it was the same story for O'Neil and his players as they succumbed to a 3-2 reverse on the South coast.
Having fallen 2-0 down in the first half, Wolves were the better side for the remainder of the contest, albeit with Goncalo Guedes' and Tommy Doyle's strikes proving to be no more than a consolation.
Guedes receives praise from O'Neil
Having gone more than 18 months since representing Wolves, there was surprise that former Benfica and Villarreal loanee Guedes remained at Molineux during the summer transfer window.
Nevertheless, the 27-year-old is now regarded as an important member of the squad, more so now that he has netted in EFL Cup games against Burnley and Brighton.
As well as talking up the possibility of Wolves' performances eventually turning into results, O'Neil was quick to pay credit to the Portugal international.
He said, as quoted by the club's official website: "I thought Guedes was excellent. He's obviously had a tough few years with injuries and being unsettled at the club.
"He showed quality, he was bright, he worked unbelievably hard for the team. There were lots of positives in there. The only thing that we can really control is the way that we perform, and the way that we perform increases our chances of getting results.
"I haven't checked, but if you go through the odds that go out before matches, I would guess we've been second favourite in all of them so far, and we probably will be for the next few as well. So, we are having to fight against the odds at the minute in the games, we're doing enough in them to give ourselves a chance of taking results and falling a little bit short.
"So, obviously, I'm disappointed with that, and I need to keep pushing to make sure that we don't come up short. As tough as the fixtures may be, we still need to find a way to get one done. But enough quality, enough good structure and enough togetherness to let you know that we're still fighting for everything, and that we're able to put results on the board."
What next for Wolves?
The games get no easier for Wolves with a trip to Aston Villa in the West Midlands derby to come on Saturday afternoon before they complete the month by playing host to Liverpool a week later.
Brentford away is the final fixture before the October international break, Wolves then returning to action by welcoming Manchester City to Molineux.