BACKGROUND: The Physician Well-Being Index (PWBI) is a brief, valid, reliable self-assessment instrument to identify health professionals' distress and those in need of an intervention. OBJECTIVE: to evaluate the construct, predictive validity (of depression, suicidal ideation, insomnia, and generalized anxiety), and internal consistency of the 7-item Spanish version of the PWBI (PWBI-S). METHODS: out of a national population of approximately 1 million Mexican healthcare professionals, a sample of 3506 subjects (42.0% physicians, 28.7% nurses and 29.3% psychologists) completed an online survey between 17 April and 7 May 2020, at the time of the COVID-19 case cluster transmission scenario in Mexico. RESULTS: In the three sub-samples, PWBI-S's Confirmatory factor analyses (adding residual covariances) exhibited adequate goodness of fit indices for the PWBS original unidimensional model. Overall Cronbach's alphas were 0.89 for physicians, 0.90 for nurses, and 0.86 for psychologists. Univariate logistic regression models showed that a cutoff point of 3 on the total score of the PWBI-S was generally related to the presence of depression, suicidal ideation, and insomnia, but not with generalized anxiety among nurses and psychologists. When trying with a cutoff point of 3, a relationship with GA was shown in psychologists, but not in nurses. CONCLUSIONS: our findings suggest that PWBI-S is a valid, reliable measure for clinical and research purposes in the field.