The Black Cats' trip to east London will be their third away fixture in four games, but while they are unbeaten after draws against Arsenal and Swansea on the road and Liverpool last weekend at the Stadium of Light, O'Neill's men are yet to get their first victory on the board.
The Sunderland boss knows Sam Allardyce's West Ham will provide a stern physical test, with his teams renown for a robust playing style and reliance on long-ball tactics and the set-piece.
"They've got off to a very good start and they will be pleased with that," O'Neill said.
"They have obviously got points on the board and they mean a great deal to any football club, but it will be tough. Knowing the manager as I do, those difficulties will be for us on Saturday and I think it will be a really difficult game for us.
"West Ham got up last season and that's not an easy league to get out of. They did very, very well.
"You would always back Sam to have taken the team up and with him at the helm I don't think there will be any danger of the team going back down again. He's proved his worth over the years."
Allardyce has often received criticism for the style of play he brings to clubs, but O'Neill dismissed the negative attitude to the route-one approach, especially when it can be so effective.
He said: "There was a game played on Monday night between Everton and Newcastle which was a very exciting game and both teams used that tactic at times.
"It still led to exciting football. There are different ways of playing the game. Not everyone can play like Barcelona although we would all love to be able to do that.
"I see even Real Madrid deciding to go long when they were under pressure and needing to get a goal. Everyone is in the results business and if you feel that's what can get you a result and it's a legitimate tactic then why not use it?"
O'Neill approaches the game with winger Adam Johnson struggling to shrug off a thigh problem and defender Carlos Cueller having picked up a hamstring injury, while Craig Gardner looks set to continue his makeshift role in the Sunderland defence in the absence of Phil Bardsley.
Despite this, the Black Cats boss believes his players are growing in belief and confidence.
"I don't consider West Ham to be a newly-promoted team, although that's exactly what they are," O'Neill said.
"I always think of them as a big-league team and it is difficult to go there at any time.
"The players are getting more confidence about their game. Against Liverpool, particularly in the first half, we matched them, broke on them very strongly and scored a great goal.
"These things give a team confidence both individually and collectively.
"Craig's favourite position is midfield but he has adjusted to right-back very well. He's come up against a few difficult opponents in the past couple of weeks and he's coming out of it very well.
"Not only that, when he's got forward he got the goal for us on Saturday. He's essentially a midfield player who is filling in until Phil Bardsley comes back and he's happy to do so."
But O'Neill admits there is one West Ham player who he would prefer not to face - striker Andy Carroll.
The forward joined the club from Liverpool on loan in the summer and impressed on his debut against Fulham before leaving the pitch in the second half after he picked up an injury.
"He's a great acquisition for West Ham United," O'Neill said.
"He had a hamstring problem but they reckon he's making really good progress. If he will be fit for the weekend I just don't know but if he is we will just have to deal with it.
"He's a very good player and because of that I would prefer for him not to be playing."