“We have been trying to get him back to full fitness, he was very close to the Brighton game [on 2 March] but the day before he felt something again in his knee,” said Howe.
“This week he has had the same discomfort so it looks like he will have to have an operation.
“He needs a small operation to clear out some fluid and then he should be fine again.”
Botman joins defender Lewis Hall and forward Anthony Gordon on the list of absentees for the Carabao Cup final against Liverpool on 16 March.
Hall, 20, has been ruled out for the remainder of the season with a foot injury.
Gordon was sent off in the Magpies’ FA Cup fifth-round defeat by Brighton last weekend for raising hands to the face of defender Jan Paul van Hecke.
The former Everton winger will be banned for the final at Wembley after Newcastle decided not to appeal against his dismissal.
“There was no intention from Anthony. He didn’t mean to hurt anybody,” said Howe.
“But, you have to look at it and ask if there is any chance of being successful and if there is no chance then what is the point of appealing, and Anthony understands that.”