The Tottenham manager thinks it will be an unpredictable game at St James' Park on Sunday.
Many Newcastle fans are frustrated with the way the club has been in run in recent years under owner Mike Ashley, and there are reports of a planned boycott of the game by home supporters, with doubts then as to the kind of atmosphere at the stadium.
Pochettino couldn't predict whether this would help or hinder his Spurs players, positing that it could end up generating a positive response from the Newcastle side.
"You never know because sometimes the effect on the players and team maybe is positive," the Argentine said when asked on his thoughts on the planned boycott.
"Maybe sometimes the players are scared and run more than all season.
"Or maybe it is a very negative atmosphere and they feel under pressure and don't show their face.
"You never know in football how it can affect all the decisions around the team. For that it is difficult to guess what will happen on Sunday."
Tottenham are on a bad run, having picked up just four points from three meetings with clubs towards the bottom of the league. The home loss to Aston Villa will have been particularly hard to stomach seeing as former boss Tim Sherwood orchestrated it, after being discarded by Daniel Levy in the summer.
Luckily for Spurs, one team that has been in even more dire form is Newcastle United, with John Carver's side having lost five successive games. But who knows what performance those home players will put forward in what could be a vastly different St James' Park atmosphere.