Patient, Health-facility and Socio-cultural related factors associated with non-adherence have contributed to poor management of ART among HIV/AIDS clients. In Lodwar County and Referral Hospital, Turkana County, a significantly high number of clients on ARV therapy have defaulted treatment. The purpose of this study was to investigate the factors associated with non-adherence to anti-retroviral treatment in Lodwar County and Referral Hospital (LCRH), Turkana, Kenya. The study was guided by cross sectional descriptive study design where qualitative and quantitative data were collected. The research instruments used for data collection consisted of structured questionnaires, interview schedules among clients on ARV therapy and documents analysis. The sample size was obtained using the modified Fishers formula at 95% level of confidence. The Statistical package for Social Sciences (SPSS) and descriptive statistics were used to analyze the data. The findings in the study revealed that there are many patient, health system and socio-cultural related factors associated with non-adherence. From the study document analysis at LCRH there should be 5243 people on ARVs, however, as at January 2018 there were 1551 (30%) who were actively on ARVs this shows that there is 70 % default rate. The study found that, Patients’ related factors that are causing non-adherence include; lack of education, lack of support, the distance to facility, lack of food, the side effects, alcohol use among many others. The study concluded that, health facility should improve their service delivery to the patients, change attitude and conduct adherence counseling. There is need to sensitize the community members to accept the HIV+ people to enable them express their health issues. They should support them and ensure that they are trained on how to use ARVs and not seek the tradition herbs and medicine men.