Background <p>Scientific literature provides very limited evidence on the impact of gestational malaria (GM) on the health-related quality of life (HRQoL) of pregnant women. The objective of this study was to describe the HRQoL of pregnant women exposed to malaria in an endemic region of Colombia; to compare HRQoL between women with and without GM; and to understand the meanings attributed to HRQoL among women exposed to GM.</p> Methods <p>A convergent triangulation mixed-methods design (QUAN–QUAL) was used. A cross-sectional study was conducted with 400 pregnant women, and a grounded theory approach was applied to a subsample of 30. In the QUAN component, HRQoL was measured using the WHOQOL-BREF. Psychometric properties were assessed through Cronbach’s alpha, internal consistency and discriminant power using Spearman’s rho, and construct validity through exploratory factor analysis. Multivariable linear regression models were used to identify factors associated with each HRQoL domain. In the QUAL component semi-structured interviews were conducted, involving open, axial, and selective coding, following the phases of description, conceptual ordering, and theorization.</p> Results <p>Among the 400 women, 6% reported a history of malaria during the current pregnancy, and 44% had experienced malaria at some point in their lives. The psychological health domain scored highest (median: 78), while physical health, environmental, and social domains showed lower scores—particularly physical health (median: 43). Multivariate models revealed that GM, comorbidities, and rural residence were associated with poorer physical and environmental health. The qualitative component revealed that women’s concept of HRQoL is predominantly material and objective, centred on access to health care, basic needs, and social support. GM was not perceived as a significant determinant of well-being, reflecting the normalization of the disease in endemic settings. However, emerging dimensions such as experiences of healthcare and dignified treatment by health personnel were emphasized—areas not captured by the WHOQOL-BREF.</p> Conclusion <p>HRQoL among pregnant women exposed to malaria in an endemic region is significantly impaired in physical, environmental, and social domains, while psychological health appears preserved, possibly reflecting adaptive coping. GM negatively affected HRQoL, though its impact was socially normalized and underrecognized by participants. The study highlights the importance of using locally grounded approaches to better capture the lived experience of health, illness, and care in vulnerable populations.</p>