Gunners chief Arsene Wenger has been left sweating over the fitness of the star duo, who were stand-out performers in Saturday's 3-1 win over Sunderland at the Stadium of Light.
Giroud was forced off late on during Arsenal's latest victory which put them top of the Premier League table, while record signing Ozil played 80 minutes despite illness.
And now Wenger has revealed that both players are doubts ahead of Arsenal's trip to Ligue 1 giants Marseille in the Champions League on Wednesday.
"We have a few problems. Some with [Mesut] Ozil but the main one is Giroud, who has a knee problem.
"He will have a test tomorrow and hopefully he will be fit. But it will only be decided tomorrow," Wenger told the club’s official website.
It's not all bad news for the north London outfit however, with Arsenal's defensive options receiving a timely boost with the news that Per Mertesacker will be available for trip across the Channel.
"There is good news. Mertesacker will be available again after illness," Wenger added.
"He [Ozil] was ill and has some tight muscles after Saturday. But I think he will be okay. We are optimistic."
With Giroud the more likely to miss out, attention has turned to who could replace the Frenchman should the powerful frontman miss out.
One option for Arsenal is the out-of-favour striker Nicklas Bendtner, though Wenger hinted that should Giroud miss out, Theo Walcott would be given the opportunity to play in his preferred position.
"I have not really thought about it that much but the obvious solution is [Theo] Walcott. We’ll see," said Wenger.