Forwards Indra Sahdan, Noh Alam Shah and Agu Casmir will all be missing from the Group E match which the visitors will view as a must win given they currently trail Iraq and China by three points.
Noh is suspended for the clash with the 2004 Olympics semi-finalists, while Indra is still recovering from knee surgery.
Agu remains a long term absentee due to his current one-year suspension from national team duties following a contractual controversy with his club side.
However coach Radojko Avramovic is confident he can cover the loss of the trio.
"It's not the best situation to be in but we'll have to cope," he told Singapore's Today newspaper.
"In many other ways, this will be the best chance for other players to stake a claim for the positions."
The strikers likely to be called into the breach are Khairul Amri and Ashrin Shariff.
Khairul, a National Serviceman with the Police Force who scored in Singapore's shock 2-0 win over Iraq earlier in the campaign, knows the importance of the match.
"If I can score and help Singapore take all three points back home, I will be extremely happy. But it is more important for us to work as a team and ensure that we beat Iraq like we did in February," he said.
While Iraq and China hold the upper hand in qualifying all four teams in the group still have a chance of reaching the finals with two matches left.
Palestine play China in Amman, Jordan in the other Group E match on Wednesday.