Despite losing to Zulte Waregem in the play-off round, APOEL reinstated in Europa League replacing the Turkish side Fenerbahçe who were banned because of the match-fixing case related to the 2010–11 Süper Lig title.
[3] APOEL were selected by a random drawing among all the losing teams from the play-off round[4] and drawn in Group F, alongside Bordeaux, Eintracht Frankfurt and Maccabi Tel Aviv.
On matchday 4, APOEL won 2–1 against French side Bordeaux at Nicosia's GSP Stadium and secured its first ever victory in the UEFA Europa League group stages.
[5] APOEL opened their Champions League campaign with a 1–0 defeat against Barcelona at Camp Nou thanks to a Gerard Piqué's goal, but left the Catalan capital with all the plaudits following a stellar display which so nearly earned a historic result.
[6] On matchday 2, Gustavo Manduca cancelled out Lucas Andersen's opener to secure a first Group F point for APOEL, after a 1–1 draw against Ajax at GSP Stadium.
[7] On matchday 3, despite another excellent display against one of the continent's strongest sides, APOEL were left bitterly disappointed as they went down to a 0–1 home defeat at the hands of Paris Saint-Germain following a late Edinson Cavani goal, just three minutes before the end.
[8] On matchday 4, APOEL fell to a 1–0 defeat against Paris Saint-Germain at Parc des Princes, as Edinson Cavani was again the difference between the two teams, scoring the only goal of the match after just 56 seconds.
[9] On matchday 5, Barcelona proved too much for APOEL as the Catalan giants cruised to a 4–0 win in a night that belonged to Lionel Messi as his hat-trick in Nicosia made him the UEFA Champions League's all-time top scorer on 74 goals.
[10] On matchday 6, APOEL suffered a 4–0 defeat to Ajax at Amsterdam Arena in the battle for third place and were sent out of European competitions after finishing fourth in Group F with just one point.
On 22 October 2015, APOEL came from behind to earn their first points in Group K after beating Asteras Tripoli 2–1 at GSP Stadium, thanks to goals by Fernando Cavenaghi and Carlão.
On matchday 4, APOEL's chances of making the knockout phase of the Europa League were dealt a huge blow as they suffered a 2–0 defeat at the hands of Asteras Tripoli at Theodoros Kolokotronis Stadium.
[15] APOEL got their Europa League group stage campaign off to a winning start after coming from behind to beat FC Astana 2–1 at GSP Stadium.
On matchday 4, APOEL achieved an important 1–0 victory over Young Boys at GSP Stadium and made a big step towards their qualification to the knockout phase of the competition.
On matchday 5, APOEL made history after becoming the first Cypriot club to reach the knockout phase of the UEFA Europa League, despite losing 2–1 away to FC Astana.
[17] Despite being one of the seeded teams, APOEL handed a tough draw in the UEFA Europa League round of 32 as they were drawn to face Basque giants Athletic Bilbao.