Olympiacos struck late in the first half to hand West Ham the first setback of their Europa League campaign with a 2-1 victory on Thursday.
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Lucas Paqueta volleyed home in the 87th minute but the Premier League club couldn't find an equaliser after captain Kostas Fortounis and Brazilian defender Rodinei scored before half-time in Greece.
Olympiacos snapped an 11-game winless run in the competition going back to 2021.
With goalkeeper Lukasz Fabianski ill, Alphonse Areola got his first start in Europe for West Ham since the Europa Conference League final in June.
Hammers boss David Moyes defended his team selection after the loss after making seven changes in the Greek capital with one eye on Sunday's visit of Everton.
"Look, we changed a lot of players tonight, we've got the Premier League coming up and we've got a League Cup game next week and we'd won the first two games in the group, which gave us leeway to make changes tonight," Moyes told whufc.com.
"But maybe I have to recognise that while we didn't win the Conference League games easily, as they were all tough games, coming to Olympiacos after winning away in Freiburg - which was a good result - this wasn't a good result and wasn't a good performance.
Freiburg joined West Ham atop Group A with six points after a 3-1 win at Serbia's TSC Backa Topola. Olympiacos are two points behind while TSC remain on one point.
Amine Harit and Jordan Veretout both scored from the penalty spot in Marseille's 3-1 home win over 10-man AEK Athens in the first victory for the French club.
Vitinha, preffered by coach Gennaro Gattuso to Pierre-Emerick Aubameyang, put the hosts in front in the first half. Orbelin Pineda equalised in the second before Harit and Veretout secured the win.
AEK goalkeeper Cican Stankovic was sent off for a foul in the box.
Forward Luis Muriel's two goals helped Atalanta draw 2-2 at Sturm Graz and top Group D with seven points. Sporting got a 1-1 draw at Rakow in Poland.
Rangers and Sparta played to a goalless draw in Prague to place two points behind Group C leaders Real Betis, who won 1-0 at Aris Limassol.
In the third-tier Conference league, Aston Villa routed AZ Alkmaar 4-1 in the Netherlands.
Leon Bailey and Youri Tielemans scored in the first half with Ollie Watkins and John McGinn netting after the break. Ibrahim Sadiq scored a consolation goal for the hosts.
Australian Associated Press