The Lilywhites required a late goal in the original tie and now have an unwanted extra fixture to contend with, three days before taking on Arsenal in the Premier League.
As well as having a North London derby to prepare for, Spurs also face Juventus in the Champions League last 16 in a week's time, leaving Pochettino with little doubt that he needs to chop and change his personnel.
"We are going to rotate the starting XI, for sure," he told reporters at his pre-match press conference. "I cannot tell now, like always, but of course we need to rotate, we need to use players that don't play too much. We are having a very busy period, and we need everyone fit and available to play.
"For us, we have to be focused on Wednesday, but after Sunday, Wednesday, a lot of players play a lot of games. For me, we have a squad good enough to win. Of course that will be tough. That is why for me it is not important the names that are going to play tomorrow.
"When you have a squad like we have, it will be very good for some players to show their quality, and it is a great opportunity for them to show that they can fight for a place in the Premier starting XI. For me, it is the same whether tomorrow is Newport or another Premier League team.
"We take the competition very seriously, and tomorrow we are very focused and convinced that we are ready to win and compete. I think it is a game that we must win."