Shamrock Rovers were beaten 3-0 at Gent in their Europa Conference League tie on Thursday night.
The League of Ireland side had been looking to build on a goalless draw at home to Swedish club Djurgardens in their opening Group F tie.
The Belgians, though, proved too strong as goals from Hugo Cuypers and Vadis Odjidja-Ofoe saw them 2-0 up inside 18 minutes.
Midfielder Odjidja-Ofoe, who had a spell in England with Norwich, added a third with a curling shot just after the hour.
Djurgardens beat Norwegian side Molde 3-2, leaving Shamrock Rovers bottom of the group.
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Elsewhere, Fiorentina lost 3-0 at Istanbul Basaksehir, while Scottish club Hearts won 2-0 at Latvian side RFS.
A first-half penalty from Lawrence Shankland put the Jambos ahead, with Alan Forrest sealing victory in stoppage-time to put Hearts second in Group A.
West Ham top Group B with a 100 per cent record after coming from behind to beat Danish side Silkeborg 3-2.
Kasper Kusk had put the hosts ahead early on, before Manuel Lanzini equalised from the penalty spot.
Gianluca Scamacca and a header from Craig Dawson made it 3-1 to the Irons going into half-time, but Soren Tengstedt’s late goal gave Silkeborg hope.
In the Europa League, Manchester United won 2-0 at Sheriff Tiraspol with a first-half goal from Jadon Sancho and Cristiano Ronaldo’s spot-kick.
Real Sociedad, who won at Old Trafford last week, sit top of Group E after their 2-1 victory over Omonia Nicosia.
Italian side Lazio went down 5-1 at Midtjylland in Group F, while Feyenoord saw off Sturm Graz 6-0 at De Kuip with a brace from Iran forward Alireza Jahanbakhsh.
Bundesliga leaders Union Berlin lost 1-0 at Braga, who top Group D. In Group H, French side Monaco were beaten 1-0 at home Ferencvaros.
Bodo Glimt battled to a 2-1 win over Zurich, which sees the Norwegians lead Group A, with Arsenal’s tie against PSV Eindhoven having been postponed because of lack of available police in London during the national period of mourning following the death of the Queen.