With the Carabao Cup final looming, Howe admits they didn't want to risk aggravating an injury Isak had picked up going into the game.
Howe said: "It goes without saying how important he (Isak) is to us. I thought you could see that today.
"It was a late decision, around midday today. He just didn’t feel right with his groin, so we didn’t want to take the risk – we’ve got too many big games to come."
Howe added: "I had a chat with him around lunchtime to see how he felt. We knew he was feeling something yesterday. We hoped that it would improve overnight, but it didn’t improve enough."
Newcastle expect Joelinton and Sven Botman to be back for the weekend clash with Brighton.
Howe said: "I think they’ll be there or thereabouts for Sunday. That would be a massive boost. It’s difficult to say because they haven’t trained with the team yet, but fingers crossed."