Following the WHO’s global pandemic declaration and Uganda’s confirmation of its first COVID-19 case in March 2020, a set of guidelines and directives were given to prevent the spread and mitigate the effects of the novel coronavirus. While initial strict enforcement was ensured and adherence to these preventive guidelines registered, it rapidly declined within a few weeks. This paper uses the ecological systems theory and COM-B model to explore adherence barriers and facilitators. We used data from a mixed methods cross-sectional study conducted in two slums within Kampala, Uganda’s capital city. Study participants were 807 (660=quantitative, 147=qualitative). For data collection we used interviews, focus group discussions, observation and a community survey. Quantitative data was collected using ODK, cleaned, coded in excel and transferred to SPSS for analysis. Qualitative interviews were audio recorded, transcribed, coded and thematically analysed using NVivo12 software. Study findings show high and varied levels of non-adherence with hand washing at 52.7% and disinfection of touch surfaces at 9.9%. Non-adherence was attributed to a number of economic, sociocultural, political and structural reasons. Despite availability of prevention opportunities, weak capacity and low motivation led to largely undesirable behavior which increased the risk to COVID-19 infections among slumdwellers. The COM-B model can be used to better understand critical intervention pathways to increase adherence to policy and adoption of health protection behavior among vulnerable communities. It is possible to institute adherence barriers among slum dwellers through simple policy and programming responses if contextual factors are recognised.