Kenya runs a robust Prevention of Mother to child Transmission (PMTCT) of Human Immunodeficiency virus (HIV) Program. Early Infant Diagnosis (EID) supports PMTCT. Human Immunodeficiency virus exposed infants are either put on prophylaxis or antiretroviral therapy (ART) treatment depending on their HIV status. However, the extent of adherence to treatment in HIV exposed infants in low resource setting is unknown. Factors, which affect adherence to treatment in Mumias region, are unknown. To address this knowledge gap, this study aimed at determining the factors that affect adherence to treatment in HIV exposed infants in selected Early Infant Diagnosis (EID) sites in Mumias region, Western Kenya. This was a cross-sectional analytical study. The number of missed appointments defined adherence. The respondents were caregivers with HIV exposed infants. Variables collected using questionnaires included age and sex of the caregiver, level of education, income level, occupation, religion, marital status, number of children, children infected, HIV status of the infant, cost associated with access to the health facility. A univariable regression model was used to describe relationship between various variables and adherence to treatment. The study enrolled 384 participants who presented their HIV exposed infants in health facilities for treatment and care. The Roche Amplicor_ HIV DNA PCR kit was used to test for HIV status of the exposed infants. The health facilities include St. Mary’s Mission Hospital, Mumias Model Health Centre, Mumias Sugar Clinic, Matungu Sub-County Hospital, Bukaya Health Centre, Malaa Health Centre, and Makunga Health Centre. The study recruited per health facility, as follows 116, 35, 60, 89, 32, 21 and 31 respectively. Nearly all (97.9%) the participants were female and 85.4% of them were married. Their age ranged from 15 to 66 years. The mean age was 32.8 years with a median age of 33 years. More than half (66.7%) of the respondents were Christians, 31.8% of them were Muslim and 0.5% were traditionalists. Majority (71.9%) of the participants reported social stigma from friends, family and community. On the other hand, 12.5% of the respondents lacked formal education while 53.9% of them attended primary school, 25.5% of them completed secondary education. Only 8.1% of the respondents had attained tertiary education. Majority (60.7%) of the xii participants had one child while the rest (35.4%) had more than one child under their care. This was separate from the HIV exposed infant recruited in the study. According to the study responses, more than half (56.3%) of the respondents were employed. In terms of EID education, nearly all (95.7%) the respondents had undergone training on the importance of EID to HIV exposed infants. According to the study responses, 95% of the respondents who earn less than 500 shillings a month had to have at least 51 shillings for them to access treatment in terms of transport. In terms of transport, respondents who earn more than 3000 shillings a month had to incur at least 40 shillings as transport cost. Laboratory results indicated that 5.2% (20 out of 384) of the HIV exposed infants were HIV positive. Nearly half (49.8%) of the HIV exposed infants adhered to treatment. The odds ratio of non-adherence in a respondent who had any ill child was 5.3 (95%CI, 1.6-18.3, P<0.05). Similarly the odds ratio of adherence among respondents with four children under their care was 2.7 (95%CI, 1.0-6.8, P<0.05). Respondents who used less than Ksh.50 as transport cost were more likely to adhere to treatment (OR 1.7, 95% CI 1.1-2.6). Respondents who were given monetary assistance from family members or spouse were less likely to adhere to treatment (OR 0.5, 95%CI, 0.20-0.99, p<0.05). Several factors like transport cost to the health facility, presence of any other ill child, number of children and monetary assistance affect adherence to treatment in HIV-exposed infants. Therefore, efforts must concentrate on addressing the needs that reduce vulnerability of life groups such as infants and women in terms of HIV.