The prevalence of chronic medical and psychiatric diseases has continued to increase worldwide, and their consequences have remained a growing concern. Acting with a number of sociodemographic and clinical variables, they tend to affect quality of life (QOL) and onward to life expectancy. There is a direct relationship between QOL and life expectancy. Hypertension and diabetes mellitus acting with adverse environmental factors reset and overamplify the sympathetic outflow, and this may worsen hypertension and or cause depression, dysthymia, and anxiety disorders. Tuberculosis and HIV are two chronic infective medical conditions that equally negatively affect quality of life well-being and life expectancy. These chronic medical and psychiatric conditions have been associated with reduced QOL and life expectancy. The aim of this study, therefore, was to determine the impact of chronic medical and psychiatric disorders (HIV, tuberculosis, diabetes mellitus, hypertension, dysthymia, and GAD) on quality of life and life expectancy. Following ethical approval and informed consent from the participants, 40 subjects from each group of HIV, tuberculosis, diabetes mellitus, hypertension, anxiety, and dysthymia were studied using sociodemographic/ clinical questionnaire and the WHOQOL-Bref. The data were analyzed using the SPSS version 20 statistical package. Confidence interval was set at 95% while P-value of less than 0.05 was considered statistically significant. There was reduced QOL on physical, psychological, and social relationship, environment domains, and general health facet, respectively. Chronic medical and psychiatric conditions may contribute to reduced QOL and life expectancy. Management of patients with these conditions should necessarily include attention to their QOL and well-being.