Van Persie has been instrumental in Holland's run to the last four of the tournament, but he had to train separately from his team-mates yesterday after complaining of a stomach problem.
Coach Louis van Gaal confirmed in Sao Paulo that his star striker, who has scored three goals in Brazil, is a serious doubt for the last-four clash.
"He has a stomach problem, an intestinal problem. I don't know [if he will play]," Van Gaal told a press conference.
"I will decide [on Wednesday]. Van Persie is our captain, so he is very important to us.
"In principle my captain always plays, but he has to be fit."