The 2021 season was Santa Cruz's 108th season in the club's history.

Santa Cruz competed in the Campeonato Pernambucano,[3] Série C[4][5] and Copa do Nordeste.

[6] Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply.

Players may hold more than one non-FIFA nationality.

Source: Santa Cruz official website (c) Indicates the caretaker manager