Abstract The Patient Health Questionnaire-4 (PHQ-4) is an ultra-brief screening instrument to measure depressive and anxiety symptoms. This study evaluated the dimensionality and reliability of the online version of the PHQ-4 in a large sample of the general population in Colombia. Data were collected during the first phase of lockdown measures occasioned by the COVID-19 pandemic. A total of 18,061 adult participants completed the online version of the PHQ-4. The characteristics of the items and subscales were explored. Dimensionality was examined using confirmatory factor analysis (CFA), including an examination of invariance (configural, metric, and scalar) across socio-demographic characteristics. Reliability indices were computed and known-groups validity was addressed by estimating associations between PHQ-4 scores and socio-demographic characteristics. The CFA showed significantly adequate fit indices for the expected two-factor structure, being invariant across gender, age, income level, education level, and region. Internal consistency was satisfactory for the PHQ-2 ( α = .83), the GAD-2 ( α = .79), and the PHQ-4 ( α = .86). Higher scores on depressive (PHQ-2), anxiety (GAD-2), and psychological distress (PHQ-4) symptoms in females and young people, and those respondents with lower income, unemployed, and lower level of education were observed. The findings indicate that the PHQ-4 is a reliable scale for depressive and anxiety symptoms among adult Colombian people, being recommendable this tool for online surveys.