Spartak Moscow Dutch winger Quincy Promes (AFP)
A much-changed Leicester went down 1-0 to Legia Warsaw in Poland, while Napoli's unbeaten record this season was ended by Quincy Promes' double for Spartak Moscow in a thrilling 3-2 win for the Russians at the Diego Maradona stadium.
Unlike the Italians, who top Serie A with a 100 percent record, Leicester have also gotten off to a poor start domestically in the Premier League.
With that in mind Brendan Rodgers made wholesale changes ahead of Sunday's trip to Crystal Palace and paid a heavy price.
The only goal of a cagey encounter in Warsaw arrived on 31 minutes as Mahir Emreli shrugged off Daniel Amartey and drilled a low shot through Jannik Vestergaard's legs and in off the post.
Napoli's comeback from 2-0 down to draw 2-2 at Leicester two weeks ago had put Luciano Spalletti's men in a good position to progress to the last 16 as group winners.
And they made a fast start on Thursday as Elif Elmas struck after just 11 seconds.
However, Mario Rui's red card on 29 minutes changed the course of the game.
Promes levelled early in the second period and Mikhail Ignatov put the visitors in front before Maximiliano Caufriez's dismissal balanced up the numbers.
Another goal from Promes in stoppage time put the game beyond Napoli despite Victor Osimhen pulling back a consolation deep into stoppage time.
Legia top the group on six points with Spartak on three and the more fancied Leicester and Napoli left on one each.
Rangers' poor European form also continued as Steven Gerrard's men went down 1-0 to Sparta Prague in a match overshadowed by booing of Gers' midfielder Glen Kamara.
The Finnish international was racially abused by Slavia Prague defender Ondrej Kudela last season, which earned the Czech international a 10-game UEFA ban.
The Letna Stadium was originally meant to be shut for Rangers' visit following a separate racist charge against Sparta after Monaco's Aurelien Tchouameni was subjected to abuse in August.
UEFA instead agreed to a proposal for the game to go ahead in front of mainly schoolchildren with some accompanying adults, but booing was audible any time Kamara touched the ball.
David Hancko's first-half headed goal condemned Rangers to a second consecutive defeat in Group A before Kamara was sent-off with 15 minutes remaining for two bookable offences.
Toko Ekambi scored twice for Lyon as they thrashed Brondby 3-0 to stay top of the group with maximum points from two games.
In Group B, Real Sociedad and Monaco played out a 1-1 draw in San Sebastian, while PSV Eindhoven moved to the top of the section with a 4-1 win at Sturm Graz.
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