Barca have already booked their qualification into the knockout stage as the winners of Group B and Valverde has confirmed Luis Suarez, who returned from injury in this weekend’s 4-0 derby win at Espanyol, will be left out.
However, the manager was not clear as to whether those changes will include Messi, who scored two goals and added an assist in the derby victory.
Messi is enjoying a run of 12 straight games with either a goal or assist for Barcelona – a streak only interrupted by his shoulder injury sustained against Sevilla that kept him out three weeks.
And his return from injury and short turnaround is precisely the reason Valverde is concerned, though he stopped short of promising his star man would sit.
"Sure there will be changes. Players need rest and we had a tough match last Saturday," Valverde told reporters. "[Tottenham] are going to bring their best players, not necessarily something that we can do. The players have some discomfort so I have to take that into account.
"After being without him [Messi] for several games I don't know if we'll have him out there for two games in three days. But Luis Suarez is definitely not going to play."
Though reporters pressed Valverde on Messi's status, he refused to elaborate further, adding: "I will tell you in 24 hours when I announce the team.
"The important thing is the players who come out of the dressing room are motivated and ready to play. They're facing a team that has everything riding on the line.
"There's nothing to fear but it's not that different from the match at Wembley. Players will have to play their best to win tomorrow and I have no doubt about that."
Valverde suggested Jasper Cillessen could start in goal in place of Marc-Andre ter Stegen and indicated Arthur may also return from injury against Spurs.