While the European nation are sweating over the fitness of skipper Vincent Kompany and fellow defender Thomas Vermaelen, the USA enter the game hoping to have main striker Jozy Altidore back in their ranks.
Belgium, who cemented their place among the tournament favourites in a Group H campaign that brought a maximum haul of nine points, were able to overcome South Korea without Kompany last time out.
However, they will be desperate to have their inspirational captain back from abdominal and groin problems in Salvador.
Should Kompany not make it, the spotlight will fall more closely on Vermaelen, who is suffering from a hamstring issue and has managed just 31 minutes of action in the competition.
Whether they are fit or not, history suggests tha a Belgium loss is unlikely while Thibaut Courtois is between the sticks.
The Chelsea goalkeeper has yet to taste defeat in 20 international appearances and is naturally hoping to keep that record up for some time yet.
"Of course it's great that I've never lost with the Red Devils and long may it last," said Courtois.
The 22-year-old also warned that, despite their fine record, Belgium have yet to click into top gear.
"Maybe we haven't yet reached the standards here that we know can but we still got nine (points) out of nine," he added.
"If we don't play superb football against the US but still win, that'll be good enough for me. I'd much rather we not play the perfect World Cup match than go home."
US coach Jurgen Klinsmann is optimistic of being able to call upon the services of Altidore, who strained his hamstring versus Ghana in the opening game.
The Americans have impressed in his absence, drawing 2-2 with Portugal - who required a last-ditch equaliser - before being edged out 1-0 against Germany.
However, the physical presence brought by Altidore offers an all-important variety to a side who have already defied expectations just by reaching the second phase.
Midfielder Michael Bradley said: "Getting out of that group is certainly a positive thing, but the feeling still has to be that we've not done anything yet.
"To come all this way and to come out of the group, only to then lose the first game, is disappointing for sure.
"We're only now thinking about Belgium and what's coming up, and we're excited about the pressure that comes with it."
The sides have met five times, with Belgium triumphing in four and the only US win coming 84 years ago.
The most recent contest was a friendly in May last year, Wilmots' men winning 4-2.
