Background: Severe acute malnutrition(SAM) is one of the major public health problems in developing countries including Ethiopia specifically in Afar having an overwhelming consequence on the survives of several children under five-years of age. This study intends to identify the determinants of SAM among 6-59 months of children at Dubti referral hospital, Afar Regional State, EthiopiaMethods: An institution-based unmatched case-control study was conducted in Dubti referral Hospital from March

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... to May 15, 2018. The sample size was calculated using Epi-InfoTM version 7.2.2.6 Statistical software. Using cases-control (1:2), the total sample size was 297(cases 99, controls 196). A systematic random sampling technique was used, data were collected using interviewer-administered structured questionnaire, entered in Epi-info TM, and analyzed using SPSS 21 version using binary logistic regression, with P < 0.05 considered significant. Result: The response rate was 100 % (297), mean age of the cases and controls was 14.8 months (SD ± 7.9) and 26.9 months (SD ± 15.9), respectively. Of the participants, 58.58% were male, 85.4% were Muslim, and 65.65% were of Afar ethnicity. SAM was significantly associated with children aged 6-11 months and 12-23 months adjusted odds ratio (AOR)=4.3, 95%CI 3.64-6.73, 11.2, 95% CI 7.89-14.5), respectively. Rural residences (AOR=2.8, 95% CI 2.62-5.73), and low monthly family income (<$30) (AOR=3.8, 95% CI 2.97-4.87) were independent predictors of SAM. This study revealed low ANC visits (32.2%), low exclusive breastfeeding practices (34.9%), and low vaccination coverage (29.6%). Conclusion: Children aged 12-23 months, rural dwellers, and low monthly family income (<$30) were identified as independent predictors of SAM. This study revealed low ANC visits, low exclusive breastfeeding practice, and low immunization coverage. Hence, cooperative efforts are needed to increase promotion of enhanced child caring practices specifically, child and maternal feeding practices, and ANC follow up and vaccination practice.