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Psychosocial factors are associated with the well-being of university students, influencing their academic demands, degree of autonomy and control, and perceived support within their learning environment. Based on the demand–control–support model, the Questionnaire of Psychosocial Factors in University Environments (CFPAU, for its acronym in Spanish) was developed. This newly created instrument was designed to assess risk and protective factors in university students. This study included a total sample of 1221 Mexican students from two public universities in Mexico. The samples were randomly divided into two equivalent groups. Exploratory factor analysis (EFA) was performed on the first group (n1 = 611), and confirmatory factor analysis (CFA) was performed on the second group (n2 = 610) via the diagonally weighted least squares (DWLS) method. The final structure consisted of 5 global dimensions and 13 specific subscales, including psychological demands, active study and professional development opportunities, institutional quality and social relationships, recognition and career certainty, and school–life conflict. The CFA results showed adequate fit across the five dimensional models (CFI range = 0.921–1.00; TLI range = 0.910–1.00; RMSEA range = 0.000–0.065; SRMR range = 0.003–0.072). Factorial invariance by sex showed stability in the configural, metric, and scalar models, and subscale reliability was adequate (α and ω = 0.71–0.90). Furthermore, convergent and divergent validity were verified through correlations in the expected direction via the WHO-5 and DASS-21. These findings support the structural validity and internal consistency of the CFPAU, confirming its usefulness in identifying psychosocial risk and protective factors in university students.