Maddison scored a superb opener in Monday's 3-1 victory over Coventry City, making his first start in 536 days after a lengthy injury absence.
However, the 29-year-old has not trained with his team-mates in the three days since that match, leaving De Zerbi with a decision to make before the trip to Stamford Bridge.
"In the first three days after the Coventry game, Maddison didn't work with us. I don't know if he's ready for tomorrow," De Zerbi said on Friday.
"I don't want to take risks because if you analyse this period of football you can see many injuries, not just for Tottenham."
Spurs have received a boost with Pedro Porro, Andy Robertson and Omar Marmoush available for selection, giving De Zerbi more options as he considers his starting line-up.
"We can also play with Mathys Tel, with Omar Marmoush inside, with (Conor) Gallagher. We have more solutions considering Pedro Porro can play," the Italian said.
Tottenham will still be without winger Savio and midfielder Lucas Bergvall, while Dejan Kulusevski remains uncertain after making his first appearance in 526 days as a late substitute against Coventry.
Defender Destiny Udogie is also sidelined with a knee problem and has not played since the 1-1 draw against Manchester United earlier this month.
De Zerbi believes Tottenham have enough depth to manage their injury concerns, stressing that the priority is to make the right decisions for both the players and the team.
"We are lucky because in the same position we have many solutions," he said. "We have to find the best for him and the best for us."
The challenge against Chelsea will be considerable. Tottenham have won only once in their last 36 Premier League visits to Stamford Bridge and have managed just one victory in their last 41 trips there in all competitions.
Spurs sit 16th in the table with six points, while fourth-placed Chelsea have 13 points and are targeting a seventh consecutive league victory over their London rivals for the first time.
De Zerbi, however, wants Tottenham to use their poor record as motivation rather than allowing it to undermine their confidence.
"For me, it's one motivation more for the players," he said.
"I want this negative record to give us more motivation, mentality and energy to win a game. We have the qualities to win this game."
Nigerian international Alex Iwobi's versatility and quality have earned high praise from Coventry City manager Frank Lampard, who believes the Fulham midfielder was already a good player before their time together at Everton.
Bradley Barcola is available for Liverpool's Premier League meeting with Brighton at Anfield on Sunday, but Dominik Szoboszlai has been ruled out as the Reds continue a demanding run of fixtures.
Arsenal manager Mikel Arteta could hand Max Dowman an increased role in the first team after Bukayo Saka was ruled out for up to eight weeks with a quad injury.
Manchester United head coach Michael Carrick will be looking for an immediate response when his side host Bournemouth at Old Trafford, after their humiliating Champions League defeat to Como.
