The Perceived Stress Scale-4 (PSS-4) is an ultra-brief self-report measure to assess perceived psychological stress. This study evaluated the psychometric properties of the PSS-4 in Colombia. A total of 1911 adult participants with university education completed the PSS-4. Characteristics of the items and the subscales were explored. Dimensionality was assessed using confirmatory factor analysis (CFA), incorporating an examination of invariance (configural, metric, scalar, and strict) across socio-demographic characteristics. Construct validity (convergent and discriminant), reliability indices, know-groups, and predictive validity were also computed. The CFA showed adequate fit indices for the two-factor model (hopelessness and coping), being invariant across gender, income level, age, and work status. Internal consistency was adequate for the PSS-4 (α = .73, ω = .72, λ2 = .74). Significant positive correlations of the PSS-4 were identified with depression (r = .59) and anxiety (r = .55), as well as significant negative with post-traumatic growth (r = -.37) and resilience (r = -.47). The PSS-4 showed adequate capacity to predict potential depressive and anxiety symptoms, as well as protective factors such as resilience and posttraumatic growth. Higher scores on the PSS-4 were observed among young people, as well as among people with lower incomes and those unemployed. These findings suggest that the PSS-4 can be a reliable and valid tool for assessing psychological stress in Colombians with university education.