Gayle, 27, scored 23 goals to fire the Magpies back into the top flight last season but is still to get off the mark this term. The striker came off the bench in the 68th minute of last Sunday's 2-2 draw at Southampton to replace Joselu with Rafa Benitez hoping the striker could help his side see out a victory. But the substitute suffered a calf injury not long after his introduction and struggled through the rest of the match.
Speaking after that draw, Benitez confirmed his striker had suffered a calf problem and speaking at a press conference on Friday, the Spaniard confirmed he is not in contention ton take on his former club at St James' Park.
"Gayle had a little problem with the calf. It is not serious, but he is not ready for this game," Benitez said.
Newcastle also remain without full-back Paul Dummett due to a hamstring problem but Massadio Haidara has returned to training having recovered from a knee problem.
Talk of a takeover on Tyneside continues to dominate the news agenda at Newcastle with recent reports suggesting the club have found at least one potential buyer ready to take the club off Mike Ashley's hands.
Typically however, Benitez insisted he and his side are not being distracted by off-the-field issues and are fully focused on the visit of Palace.
"I spoke to (managing director) Lee Charnley and he told me he had no news on that," Benitez said. "There is nothing I can do about that, so I will do my job."
He added: "I spoke to (managing director) Lee Charnley and he told me he had no news on that. There is nothing I can do about that, so I will do my job."