ABSTRACT Background: There are over 36.9 million people globally living with HIV/AIDS, 35.4 million people have died from AIDS-related illnesses since the start of the epidemic and Sub-Saharan Africa carries 70% of the global burden of infection. While there has been a gradual increase in the number of HIV/AIDS patients accessing treatment, 33% of adults living with HIV/AIDS are still not on Antiretro-viral treatment. It’s possible that the challenges faced by HIV/AIDS patients are probably not yet fully addressed beyond provision of ART since a significant proportion of patients legible for ART are still not enrolled on treatment and the of HIV/AIDS related morbidity and mortality continue to be severe. The study therefore thought to establish whether socio-economic and institutional factors have a bearing on challenges faced by patients receiving ART at Kiryandongo general hospital. Methods: Between January 2018 and December 2018, a cross-sectional study, descriptive in nature and employing both qualitative and quantitative research designs was conducted at Kiryandongo general Hospital ART clinic with 201 respondents. Interviewer administered questionnaires were used to ascertain socio-economic and institutional challenges experienced by patients receiving ART Results; A total of 201 participants were consecutively enrolled into the study. Majority of the respondents were in the age bracket of 26-35 years and peasants. The findings indicated that depression, Stress, stigma, discrimination, lack of family support, disclosure of sero-positivity and sexual problems were social challenges experienced by patients receiving ART. Economic challenges reported were; Low monthly income, transport expenses, food expense, inadequate general life economic demands like basic needs. The Institutional challenges identified were Medication/ART stock outs, long patient waiting hours, poor attitude of some staffs, inadequate clerking and counseling rooms, short intervals of ART refill and lack of community based ART services. Conclusion; Socio-economic and institutional challenges are real among HIV/AIDS patients. There is need to empower patients and communities with better sustainable incomes through poverty eradication programs as well as improving health provision services.