Prior to the start of the 2015–16 season, Isco switched his shirt number from 23 to 22, which he had previously worn at Málaga. On 21 November 2015, as Real lost 0–4 at home to Barcelona in "El Clásico", he was sent off in the 84th minute for a foul on Neymar. He scored twice on 2 December, as the team won 3–1 at Cádiz in the first leg of the last 32 of the domestic cup. Isco was a part-time starter when the team won the 2015–16 UEFA Champions League defeating Atlético Madrid 5–3 on penalties in the final played at the San Siro, Milan.