Objective The aim of this study was to estimate values of health-related quality of life (HRQOL) by focusing on the physical and mental health of an adult population sample in the city of Barranquilla, Colombia.Materials and Methods Cross-sectional study with 368 adults representing an adult population. The questionnaires included the health-related quality of life “CDC-Healthy Days”, the Zung Self-Rating Depression Scale, and the Overall Disability Sum Score. The prevalence of fair or poor health status (FPH), frequent physical distress (FPD), frequent mental distress (FMD), and frequent activity limitation (FAL) was estimated according to socio-demographic characteristics, presence of depression, and physical disability.Results The mean age of 368 adults was 45.6 ± 18.3 years; 55.7% were males. Only 21% of this population considered their general health to be fair or poor. The prevalence of FPH, FPD, FMD and FAL was higher in women than in men, and increased with greater severity of depression and higher physical disability. Moreover, 12% of the population presented with mild depression, 3.8% with moderate depression, and less than 1% with severe depression. 94% of this population did not have an arms or legs disability.Discussion This study provides HRQOL values for an adult sample of the population of Barranquilla, Colombia. Overall, the HRQOL of this population, with subtle differences, is similar to other reports from Colombia. In general, women and people with depression and physical disabilities had a worse quality of life.