The Gunners are already three points clear at the top of Champions League Group F when they take on Napoli and so a draw would be good enough to secure first place and with it seeding for the knockout stage.
Defeat could also see Arsenal progress, depending on the final scoreline and also Borussia Dortmund's result in Marseille.
Wenger does not want his team to dwell on the frustrations of not being able to hold out for victory over Everton, which would have extended their lead at the top of the Premier League to seven points as Arsenal now head into a run of six matches in some 21 days.
The players will have little time to recover when they travel back from Italy directly after the Napoli match before tackling Manchester City at the Etihad Stadium on Saturday lunchtime.
Arsenal then go into a showdown with Chelsea on December 23 as the festive fixtures get into full swing - with the small matter of a north London derby against Tottenham in the FA Cup third round on January 4 also on the horizon.
"We will (try) to rotate a little bit at times, but never more than two or three players because the stability of the side is so important," said Wenger, who could recall England forward Theo Walcott to the starting line-up against Napoli.
"When you play so many games, sometimes in one game you have a feeling the legs are a bit tired, but sometimes the game after they surprise you again and everybody has recovered.
"At the moment we have a stable squad. In some positions I rotate more than others where the stability is important.
"But overall we have no major signs of fatigue medically."
Wenger added: "The Napoli game certainly (is decisive) as it is to be in the Champions League or not.
"The two other (Premier League) games not definitely as we are five points ahead and overall the championship is a marathon."
Wenger has warned his side there can be no complacency against Rafael Benitez's men, who need victory to maintain their own hopes of qualification in what is set to be an intimidating atmosphere at the Stadio San Paolo.
"Benitez has a very big experience, is a very intelligent manager so I know he will prepare his team well," Wenger added. "The only way we can counter that is to be at our best and put in a good performance as an average performance will not be good enough.
The Gunners boss expects his men not to be overawed by the heated reception which awaits them, having already produced smash-and-grab raids at similarly intimidating away venues earlier in this current Champions League campaign.
"When you go from Fenerbahce to Dortmund, you are used to these kind of atmospheres and we know how to deal with that," Wenger said.
Defender Laurent Koscielny echoed his manager's calls for another determined display.
"It was very difficult to win in Germany, but we showed some good character and were very strong in defence, then had the opportunity to score, which we took. On Wednesday, it will be like that again," the France international said.
"Napoli are a good team, very hard, but we want to finish in first place in the group, so we need to win here."
Arsenal, meanwhile, have increased security measures following problems caused by Napoli's "ultra" hard-core fans in previous European ties, which included damaging a pie shop near the Emirates Stadium when they travelled to London earlier this season.
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