With Isak pushing for a move, Howe conceded on Friday morning that the Swede's actions have left management disappointed.
The Toon manager began: "He won't be part of the squad this weekend.
"The club has to act in the best interests of Newcastle United. It will do that in every situation
"It looks like it is coming to an end, or it will come to an end pretty quickly.
"It is disappointing I am having to mention this at length and taking us away from the football. The players have done well to blank it all out. It is there in the background, it is regrettable that we are in this situation."
Sad moment
Isak and Newcastle exchanged public statements in midweek as the player's frustration being blocked from joining Liverpool reached social media.
Asked about the striker's decision to go public, Howe stated: "It was a sad moment. My preference is these things do not happen publicly. They are better dealt with behind closed doors. But needs must. The club has spoken and justifiably so in that moment.
"He’s contracted to us. He’s our player. My wish is that he would be playing on Monday. He won’t be and that’s regrettable. But 100 per cent I want him back in a Newcastle shirt."
Howe, expanding on the theme, also made a plea to Isak and the Toon support. Howe retains hope of his star striker staying and the relationship with the fans being fixed.
He added, “The relationship between our fans and Isak can still be good. The fans will always react to the way a player plays. There is always two sides to a story. We will see where we are in a week’s time. I hope I can work with him again”.
Liverpool can expect electric atmosphere
Indeed, moving onto the game, Howe is upbeat about hosting the Reds on Monday, knowing the home support will be up for the game given the controversy around Isak.
He said, "The first home game is always going to be electric. Under the lights, evening games are always really special for us. I have no doubt this will be a really passionate display from the home support.
"We need to use that, but not be reckless with it. We've got to concentrate and deliver our game plan, but using the energy from the crowd will be vital for us."
A bonus for Howe and Newcastle will be the availability of Jacob Ramsey, who signed on Friday from Aston Villa.
"He'll be available. We've still got training sessions to go before the game, but he's in a good place and has looked really impressive. Really, really good technically, very intelligent, and I think he'll add a lot to the team. He has standout qualities."
Gordon moves into striker role
With Isak frozen out, Howe is left without a recognised striker for the game and will continue with winger Anthony Gordon in a central attacking role.
The manager said, "He’s done it enough to do the job really well for the team. I have no issue playing him there, both as a starter and a substitute. He plays differently to other strikers, but that can be a positive.
"He’s got devastating pace, a really good work ethic, and he’s scored goals. I think he played really well last week in lots of different phases of his game."
Howe also responded to rumours that Isak would not be welcomed back by his Newcastle teammates.
He concluded: "There’s no doubt how the players will feel. I think they will feel the same way I do...if Alex decided to come and play for us, the players would welcome him back."