Spurs head to Stamford Bridge on the back of Monday's encouraging 3-1 home victory over Coventry City but have won only once there in the last 41 visits in all competitions.
The 29-year-old Maddison, who recently returned from a lengthy injury layoff, marked his return to the starting lineup by opening the scoring against Coventry with a superb strike.
"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 told a press conference.
“I don’t want to take risks because if you analyse this period of football you can see many injuries, not just for Tottenham.”
While De Zerbi is wary of taking risks with the recovering Maddison, Tottenham have received a boost with full backs Pedro Porro and Andy Robertson as well as forward Omar Marmoush all available for selection.
"We can also play with Mathys Tel, with Omar Marmoush inside, with (Conor) Gallagher," De Zerbi said. "We have more solutions considering Pedro Porro can play."
However, Spurs will still be without winger Savio and midfielder Lucas Bergvall, while Dejan Kulusevski's involvement remains uncertain after his long-awaited return from a 526-day absence as a late substitute against Coventry.
Left back Destiny Udogie also remains sidelined with a knee problem, having not featured since the 1-1 draw at Manchester United earlier this month.
"We are lucky because in the same position we have many solutions," De Zerbi said.
"We have to find the best for him and the best for us."
Tottenham, 16th in the table with six points, have won only once in their last 36 league games at Stamford Bridge where fourth-placed Chelsea, who have 13 points, will be looking for a seventh straight league win over Spurs for the first time.
"For me, it's one motivation more for the players," De Zerbi said when asked about Tottenham's abysmal record there.
"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."