ABSTRACT BACKGROUND: High incidence of malaria disease in South Sudan may be largely due to poor/non-compliance with effective treatment and preventive measures.  This study examined factors limiting/enhancing compliance with the utilization of known and effective malaria treatment and preventive measures in Wulu, South Sudan.METHODS: A case-control study involving 396 respondents was conducted. Participants were interviewed using a semi-structured questionnaire to elicit information regarding socio-demographics and factors influencing compliance with using available treatment and preventive measures for malaria.RESULTS: Respondents diagnosed with malaria reported lack of insecticide treated nets (51.5%) and forgetfulness (16.6%) as reasons for not using insecticide treated nets. About 26% of them lacked the knowledge of insecticide treated net’s usefulness, while 57.5% of them did not consider it necessary to have door/window barriers.  About 44% of all respondents forgot to take prescribed drugs at the right time while 14.5% of them did not complete drug prescriptions because they felt relief of symptoms. There were significant associations between identified factors of compliance to treatment/preventive measures and occurrence of malaria (all at p < 0.001). Having insecticide treated nets (OR: 5.78; CI: 3.46-9.00), awareness of its benefits (OR: 8.76; CI: 3.02-25.37), being taught on its use (OR: 3.35; CI: 2.17-5.18) and understanding of its use (OR: 3.80; CI: 2.01-7.20) were significantly associated with year-round utilization of insecticide treated nets.CONCLUSION: Poor access to and knowledge of malaria treatment, control and preventive measures are leading barriers to their effective utilization in Wulu.KEYWORDS: Compliance, effectiveness, malaria, prevention, treatment