This study examined the relative efficacy of social support seeking (SSS) and self-efficacy building (SEB) in the management of emotional well-being of caregivers of people suffering from HIV/AIDS. It was based at the United States President's Emergency Plan for AIDS Relief (PEPFAR) center in the University College Hospital, Ibadan, Oyo state, being the first and the largest teaching hospital in Nigeria. A 3 × 2 factorial design consisting of treatment and a control group was used. The columns have two levels of gender being male and female caregivers. One-hundred and sixty-five (165) caregivers who were taking care of people that are suffering from HIV/AIDS were purposively selected and randomly assigned to the treatment groups and control. The treatment was carried out for a period of eight weeks. Two null hypotheses were tested, both at .05 levels of significance. Data were collected with the use of standardized intruments rating scale; social support scale, general self-efficacy scale and emotional well-being scale. ANCOVA was used to establish significant treatment effects with the pretest as covariate. Even though SSS and SEB were both found to be effective in enhancing the emotional well-being of informal caregivers in this study when compared to the controls, SSS was significantly more effective than SEB in achieving this goal. Since the HIV/AIDS patients cannot be adequately cared for in the hospital settings due to severe shortages of material, personnel and time, serious efforts should be made by the three levels of the health care system viz: the primary, secondary and tertiary health care systems, to encourage the employment of the psychological management of caregivers of people suffering from HIV/AIDS. Also, the psychologists, clinical psychologists and the significant others should be encouraged to employ this psychological management in the care of HIV/AIDS informal caregivers.