Head coach Andoni Iraola confirmed the injury setbacks ahead of the Anfield meeting, with Isak suffering a thigh injury and Gakpo struggling with an ankle problem.
"Alex Isak and Gakpo won't play. They are not ready, unfortunately for us," Iraola said. "You always hope the doctor doesn't call you, but we have been unlucky."
However, neither injury is expected to keep the players out for an extended period. Iraola explained that Gakpo was dealing with pain from an ankle injury sustained during a challenge, while Isak was recovering from his thigh problem.
"They don't look like long-term injuries, but they are not ready for Sunday," he added.
With Liverpool short of attacking options, Lewis Koumas could be handed an opportunity to lead the line. Iraola expressed confidence in the youngster, while also considering alternatives who can operate as a central striker.
Bradley Barcola is among those options, having played across the front line, while Federico Chiesa could also return to contention. However, Chiesa has yet to feature in the current run of matches, and Liverpool are also waiting for Hugo Ekitike to become available.
"Even before we don't have Hugo Ekitike, who I am looking forward to having available," Iraola said. "As a number nine, we only have Koumas right now. We have some options: wingers who have played up front."
Jacquet, meanwhile, has been cleared to feature after concerns over his fitness.
"He is fit and ready to go. He will be fine; we need to train tomorrow," Iraola confirmed.
Liverpool head into the contest after winning four of their last five matches in all competitions, including a 1-0 victory over Bournemouth before the international break.
Manchester City arrive at Anfield as Premier League leaders, having won all their league matches so far. Iraola expects a demanding test but believes the occasion offers Liverpool an opportunity to measure themselves against the strongest opposition.
"It's an exciting game, at home at Anfield against league leaders. They've won all their games. They will go for it, so will we," he said.
"We have to be ready and help our supporters. I hope we are at the level."
The Liverpool coach also played down the significance of the result in the wider title race, pointing out that the season remains in its early stages.
"It's still very early, whatever happens on Sunday. Just five games," he said, while acknowledging the importance of testing his players against a side of City's quality.
Liverpool's preparations have been complicated by the injuries and a busy schedule, with a Champions League fixture to follow the City clash. Iraola admitted that limited training time means his squad must adapt quickly to changing circumstances.
"We have to adapt to injuries. Alex, and then Cody, and now this is City, then Champions League. The run of games means we have to get used to these things," he said.
