There is poor self-reported (SR) execution of infection prevention and control (IPC) among physicians and nurses. Self-Leadership is considered as important factor to enhance IPC SR-execution. This study aims to explore the associations between self-leadership and IPC SR-execution among physicians and nurses.A cross-sectional study of 26252 physicians and nurses was conducted in all secondary and tertiary hospitals in Hubei province, China. A questionnaire was designed to measure physicians' and nurses' self-leadership, which includes positive traits and negative traits, and IPC SR-execution, which includes motivation, process, and outcome.Positive traits and negative traits of self-leadership had significant positive associations with SR-execution motivation (β = 0.582, p < 0.001) (β = 0.026, p < 0.001), SR-execution process (β = 0.642, p < 0.001) (β = 0.017, p < 0.001), and SR-execution outcome (β = 0.675, p < 0.001) (β = 0.013, p < 0.001).This study recommends that healthcare institutions should focus on cultivating positive traits of self-leadership among physicians and nurses. Although negative traits of self-leadership can also promote IPC SR-execution, the association is limited and may lead to risks.Copyright © 2023. Published by Elsevier Inc.