On 29 November 2024, Van Nistelrooy was appointed manager of Premier League club Leicester City on a two-and-a-half-year deal running until June 2027 replacing Steve Cooper. On 3 December 2024, he got his first win as a Premier League manager, in his home debut game and winning 3–1 against West Ham United. Leicester then followed up the win by drawing 2–2 with Brighton at home on 8 December 2024. Following the draw with Brighton, Leicester began a awful run of form of only one win in 17 games, with a 4–0 away defeat to Newcastle United on 14 December 2024, then a 3–0 loss at home to relegation rivals Wolverhampton Wanderers. The defeat to Wolves began a run of eight losses in a row at home for the foxes without scoring, which was a new record in English football. On 20 April 2025, Leicester were relegated to the Championship after losing 1–0 at home to league leaders Liverpool. This left the Foxes 18 points off safety with five games to play and extended their run of home losses without scoring to nine games, also giving Leicester the record of the first team in top flight history to go nine games without scoring at home.