Celtic got off to a bright start, taking the lead in the sixth minute, with Benjamin Nygren latching onto Kieran Tierney’s cross from close range.
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Nygren was again involved in Celtic’s second goal in the 10th minute, intercepting a poor back pass from Vasilis Barkas and forcing Nick Viergever into an own goal.
It was the first time Celtic had taken a 2-0 lead in a major European match.
Nygren came close to getting his second of the night after curling a free kick into the bottom corner, but Barkas denied it.
The Hoops were awarded a penalty after Auston Trusty’s header hit Dani de Wit’s hand. Arne Engels stepped up to convert the penalty into the top corner.
De Wit halved the deficit on the stroke of half-time, leaving Kasper Schmeichel stuck for the penalty.
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The Danish goalkeeper then made a great save, deflecting a goal-bound shot wide of the goal, ensuring Celtic headed into the break with a two-goal lead.
Nygren picked up where he left off after the break, when the Swedish midfielder saw his shot deflected by Barkas.
Utrecht made it 3-2 after the hour when Adrian Blake beat Schmeichel from distance after a quick counterattack.
Any hope of a comeback was dashed when Trusty guided Engels’ corner into the net.
With this result, Martin O’Neill’s team finishes in 21st place in the standings and in one of the play-off places.