The world number 11 has been struggling with a cyst on his toe that was removed earlier this month.
Despite that procedure, Nishikori has continued to experience problems and the Japanese remains concerned ahead of his first-round match against world number 180 Wayne Odesnik.
"I had doubts about my decision [to play at the US Open] but I am going to take a chance," Nishikori said.
"However, to be honest I have some concerns about my physical fitness.
"I haven't had match practice and I don't know if I will be able to keep up when it comes to quick movement.
"If the pain comes back on the day of the game, I don't know if I will play.
"I don't know if I will be able to get through the first round."