The mentally ill patients have been shifted from institutions to home based care involving the family and the community than the straight in-hospital treatment. Consequently, the prevalence of mental illness is rising which is proportional to increased burden the primary caregivers’ face that affect their HRQoL. The aim of this study was to determine the Health Related Quality of Life (HRQoL) and associated factors of primary caregivers of the mentally ill patients at the largest teaching and referral psychiatry hospital in Kenya. A correlational study was used. Systemic random sampling was used to recruit 310 caregivers of mentally ill patients in the outpatient clinic. The WHOQoL-BREF questionnaire was used to assess Caregivers HRQoL. Statistical package for social sciences version 25.0 was used for analysis. Pearson was used to test relationships between variables and multivariate regression models were used to determine predictors of HRQoL. On quality rating 1-5, Majority (34.4%, mean 2.61 SD 1.05) of the participants reported poor HRQoL. Caregivers’ marital status ( .292, =0.000), relationship with the patient ( .166, =0.004) and patient gender ( .188, =0.001) significantly correlated with primary caregivers’ poor HRQoL. Patients’ review with compliance to treatment (61.5%), and health system support ( .420, P=0.000), were significantly associated with primary caregivers’ HRQoL. Specialized psychiatric and mental health professionals with policy designers to realize characteristics which impact the caregivers ’HRQoL so that intervention is done especially Psycho-education on patient care, encourage social support groups and improve health support system. Keywords: Health Related Quality of Life, Primary caregivers, mentally ill Patients.