Depression and anxiety are common mental health comorbidities found among women living with breast cancer. The presence of these mental health comorbidities results in decreased quality of life among patients. However, the indirect effects of depression and anxiety on quality of life have not been fully established. This study therefore examined the direct and indirect effects of depression and anxiety on quality of life through social support and religiosity.Using a cross-sectional survey, 205 purposively selected participants were administered measures of depression and anxiety, social support, religiosity and quality of life. The statistical package for the social sciences (SPSS) with PROCESS Macro was used for mediation analyses.Findings showed that there were significant direct negative effects of depression and anxiety on quality of life. Whereas depression had a significant negative indirect effect on quality of life through social support (b = - 0.247, 95% CI = - 0.482 to - 0.071), anxiety had a significant positive indirect effect on quality of life through social support (b = 0.142, 95%CI = 0.011 to 0.324). However, depression and anxiety did not have any significant indirect effect on quality of life through religiosity.These findings suggest that there is the need to examine the mental health of women living with breast cancer as part of the routine healthcare, and social support ties should be strengthened to improve their quality of life.