Objective To evaluate health-related quality of life (HRQoL) and its determinants in chronic low back pain (CLBP) patients in Cameroon. Design Observational cross-sectional study. Setting Tertiary hospital. Participants There were 150 eligible adults with low back pain of at least 12 weeks who provided informed consent. Of these, 136 with complete questionnaires were analysed. Outcomes HRQoL was measured using the WHO Quality of Life questionnaire (WHOQOL-BREF). Outcome measures included its four domain (physical health, psychological, social relationships and environmental) scores and two independent scores for overall quality of life (OQOL) and general health satisfaction (GH). Results Participants had a median age of 52 years, and median pain duration of 33 (IQR: 69) months. The median OQOL score was 50 (IQR: 25). After multivariable adjustment, tertiary education (β=11.43, 95% CI 3.12 to 19.75), age (β=0.49, 95% CI 0.12 to 0.87) and being a student (β=23.07, 95% CI 0.28 to 45.86) contributed to better OQOL. Age (β=0.57, 95% CI 0.10 to 1.04) and physical-type employment (β=-14.57, 95% CI -25.83 to -3.31) affected GH. Smoking (β=-20.49, 95% CI -35.49 to -5.48) and radiological anomalies (β=-7.57, 95% CI -14.64 to -0.49) affected the physical health domain, while disability (β=-0.67, 95% CI -1.14 to -0.20) and duration of pain (β=-0.13, 95% CI -0.20 to -0.05) affected the psychological domain. Income (β=14.94, 95% CI 4.06 to 25.81) affected the social domain, while education (β=9.96, 95% CI 1.41 to 18.50) and disability (β=-0.75, 95% CI -1.26 to -0.24) affected the environmental domain. Conclusions Our findings suggest that CLBP affects HRQoL and multiple socioeconomic and clinical factors influence its impact on different domains of HRQoL. Multipronged management programmes, especially those that reduce disability, could improve HRQoL in patients with CLBP.