This study examined the relationship between stigmatization and depression on burden of care among caregivers of the mentally ill patients. A total of 197 caregivers of mentally ill patients that were receiving treatment for psychiatric condition were recruited for the study from Anambra State Neuropsychiatric Hospital, Nawfia, Nigeria. The participants comprised of 54.3% males and 45.7% females who are within the age range of 18 to 65 years, mean age of 25.8 and standard deviation of 8.2. They were administered the Self-rating Depression Scale, Internalized Stigma of Mental Illness and the Burden of Care Schedule. The study made use of correlational research design and Pearson Product-Moment Correlation Coefficient statistics. Result revealed a significant correlation between stigmatization and burden of care among caregivers of mentally ill patients at (r. = .613, df = 8(188/196), F = 58.11, p<.05). Also, the second hypothesis was accepted indicating a significant correlation between depression and burden of care among caregivers at (r. = .438, df = 8(188/196), F = 58.113, Sig = .000 p<.05). The study recommended psycho education to members of the general public on the negative effects of stigmatization, mental illnesses and burden of care in order to reduce the effects of stigmatization, depression among caregivers of mentally ill patients to the barest minimum.