In between their UEFA Champions League qualifying campaign APOEL played three more friendly matches, beating 2–1 Ermis Aradippou, drawing 1–1 with Olympiakos Nicosia and winning Greek side Asteras Tripoli 3–2.
On 21 September 2015, APOEL claimed a hard-fought 1–0 win over Doxa Katokopias at Makario Stadium and moved to the top of the standings, although the three points came at a price after Carlão, Iñaki Astiz and Pieros Sotiriou all suffered injuries.
APOEL managed to break the deadlock after 69 minutes, when Constantinos Charalambides received a Fernando Cavenaghi's pass and from close range riffled the ball past Ethnikos' goalkeeper.
On 3 January 2016, APOEL suffered a second consecutive home defeat after losing 1–2 to Doxa Katokopias and dropped to the fourth place, seven points behind leaders AEK Larnaca.
Doxa nicked the three points at the fifth minute of added time when APOEL defender Mário Sérgio handled in the box and Paulinho thumped the ball past Boy Waterman from the penalty spot.
On 10 January 2016, APOEL bounced back from two consecutive league defeats by beating Aris Limassol 2–1 at Tsirion Stadium and moved up to the third place, seven points off top spot.
On 24 January 2016, APOEL continued their surge back to the top with a convincing 1–0 win over AEL Limassol at Tsirion Stadium and closed the gap on league leaders AEK Larnaca to two points.
The lead lasted just seven minutes as APOEL piled on the pressure and were rewarded when Georgios Efrem blasted the ball past keeper from inside the box after receiving Zhivko Milanov's low cross from the right.
The winner came just six minutes from time from Brazilian winger Vander who rolled the ball into an empty net after taking the rebound of Tomás De Vincenti's shoot which rattled the woodwork.
On 20 March 2016, APOEL took a huge step towards their fourth consecutive league title after crushing challengers AEK Larnaca 3–0 at GSZ Stadium and opened up a six-point gap at the top of the table.
AEK had a chance of getting back into the game in the 50th minute after referee awarded them a controversial penalty, but APOEL's keeper Urko Pardo managed to block André Alves shot from the spot.
On 2 April 2016, APOEL's twelve-game winning streak came to an end after a 2–2 home draw against Apollon Limassol and AEK Larnaca took advantage to move to within four points of the top of the table.
On 16 April 2016, APOEL moved a step closer to their third consecutive championship title as they increased their lead at the top to four points, following their 4–1 home win against Nea Salamina and AEK Larnaca's 2–2 draw against Apollon Limassol.
On 23 April 2016, under caretaker coach Giorgos Kostis, APOEL beat arch-rivals Omonia 2–0 at GSP Stadium and moved a step closer to their fourth consecutive league title, as they maintained their four points advantage from AEK Larnaca, only three matches before the end.
APOEL, which a few days ago parted ways with coach Temur Ketsbaia, had headed into the game four points ahead of AEK with caretaker manager Giorgos Kostis on charge.
André Alves had missed the game's first big chance before a mistake by AEK defender led to a quick counter-attack involving Giannis Gianniotas and Vander and finished off by Pieros Sotiriou who had rounded the goalkeeper before scoring into an empty net just before halftime.
On 7 May 2016, champions APOEL decided to rest many first-team players and saw their 17-match unbeaten run ended after suffering a 1–0 loss at Apollon Limassol thanks to a Luka Stojanović strike at the half-hour mark.
On 20 April 2016, APOEL were defeated by Apollon Limassol 5–4 in a penalty shoot-out after a 1–1 draw at Tsirion Stadium and eliminated from the Cypriot Cup final, missing a great chance to defend their title for a third consecutive season.
FK Vardar rarely threatened Boy Waterman’s goal while their own keeper Tome Pačovski was called into action on numerous occasions to foil Luís Leal, Tomás De Vincenti and Georgios Efrem.
Except some problems in finding the final touch, APOEL were always the superior team against Vardar and Tomás De Vincenti's goal on 60 minutes was enough to see them through the third qualifying round, despite Blagojče Ljamčevski's late equalizer.
APOEL got off to the worst possible start when Jakob Poulsen's resulting free-kick floated over the defence and met the head of Erik Sviatchenko who steered the ball past Boy Waterman.
The second half was a cagey affair with APOEL reluctant leak another goal, while Midtjylland players launched countless ineffective long balls into Boy Waterman's area.
Albeit under extremely difficult circumstances, APOEL secured European group stage football for the fifth time in seven seasons and a place in the UEFA Champions League play-offs draw.
Also, following the team's failure to reach the UEFA Champions League group stage, Domingos Paciência was fired two days later[1] and he was replaced by Georgian coach Temur Ketsbaia, who signed a two-year contract with the club.
Schalke had the game wrapped up inside the opening half-an-hour after goals from Joël Matip and Klaas-Jan Huntelaar, while Max Meyer and Johannes Geis had also rattled the crossbar early on.
On 1 October 2015, APOEL fell to a second straight defeat in the Europa League, going down to a 2–0 loss to Sparta Prague at Generali Arena, making the club's aspirations of reaching the next round complicated.
After just eight minutes, Argentinian Facundo Bertoglio crossed from the left to his countryman Braian Lluy who calmly placed the ball beyond Boy Waterman to hand Asteras a shock early lead.
On 5 November 2015, 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.
From that point on, APOEL began to dominate proceedings and were almost level when Semir Štilić's strike hit the post, but Asteras dealt a killer blow to their chances as they doubled their lead on the stroke of half-time after a close header by Apostolos Giannou.
Fernando Cavenaghi scored a fantastic drive after only six minutes to give APOEL an early lead, but Sparta Prague managed to equalize on the hour mark thank to a lucky deflected goal by Lukáš Juliš.