The Citizens trimmed the Reds' advantage at the top of the table to seven points with a restorative 3-1 win at Southampton on Sunday, with David Silva and Sergio Aguero notching efforts either side of a James Ward-Prowse own-goal.
De Bruyne made his first league start of the season in the Boxing Day loss at Leicester City following a pair of medial knee ligament injuries but he was absent from Guardiola's matchday squad at St Mary's.
The former Barcelona and Bayern Munich boss told a post-match news conference the Belgium star's latest setback is not as serious as his previous lay-offs, but he admitted that he is unsure if he will be available to take on Jurgen Klopp's side.
“I don't know how Kevin De Bruyne is,” the Spaniard said.
“I know it's not serious, but I don't know if he can play on Thursday.”
Guardiola conceded it will be "almost impossible" for City to retain their title if they lose to Liverpool, adding: “Of course, I think they'll drop points but not too many.”
Injury and suspension issues have led to the City manager asking players to carry out unfamiliar roles over recent weeks, and Oleksandr Zinchenko was caught out for Southampton's equaliser through Pierre-Emile Hojbjerg, who was later sent off for a rash lunge on the excellent Fernandinho.
Ukraine midfielder Zinchenko, deployed at left-back, then escaped punishment for a clumsy challenge on Ward-Prowse in the area but regained his poise to deliver a superb cross that Aguero headed home.
“Zinchenko was the best player on the pitch today,” Guardiola beamed. "Do you know why? Because after the mistake he didn't hide.
“I said to the guys at half-time, 'Learn from Zinchenko'. Everybody can make mistakes, everybody. But look at him for the reaction.”
Aguero, Riyad Mahrez and Raheem Sterling all went close to adding further goals for City and Guardiola repeated a familiar lament of asking his team to be more clinical.
“It could've been 1-6 or 1-7, you have to score the chances,” he said. “I'm pretty sure Liverpool won't give us that many chances.
“Last season we scored 106 goals, the best ever [in a Premier League campaign], but I thought we could've scored more.”