BACKGROUND: Severe wasting affects 16 million under 5's and carries an immediate risk of death. Prevalence remains unacceptably high in sub-Saharan Africa and early infancy is a high-risk period. We aimed to explore risk factors for severe wasting in rural Gambian infants. METHODS: We undertook a case-control study from November 2014 to June 2015, in rural Gambia. Cases had WHO standard weight-for-length z-scores (WLZ) < -3 on at least 1 occasion in infancy. Controls with a WLZ > -3 in the same interval, matched on age, gender, village size and distance from the clinic were selected. Standard questionnaires were used to assess maternal socioeconomic status, water sanitation and hygiene and maternal mental health. Conditional logistic regression using a multivariable model was used to determine the risk factors for severe wasting. Qualitative in depth interviews were conducted with mothers and fathers who were purposively sampled. A thematic framework was used to analyse the in-depth interviews. RESULTS: Two hundred and eighty (77 cases and 203 controls) children were recruited. In-depth interviews were conducted with 16 mothers, 3 fathers and 4 research staff members. The mean age of introduction of complementary feeds was similar between cases and controls (5.2 [SD 1.2] vs 5.1 [SD 1.3] months). Increased odds of severe wasting were associated with increased frequency of complementary feeds (range 1-8) [adjusted OR 2.06 (95%: 1.17-3.62), p = 0.01]. Maternal adherence to the recommended infant care practices was influenced by her social support networks, most importantly her husband, by infant feeding difficulties and maternal psychosocial stressors that include death of a child or spouse, recurrent ill health of child and lack of autonomy in child spacing. CONCLUSION: In rural Gambia, inappropriate infant feeding practices were associated with severe wasting in infants. Additionally, adverse psychosocial circumstances and infant feeding difficulties constrain mothers from practising the recommended child care practices. Interventions that promote maternal resilience through gender empowerment, prioritising maternal psychosocial support and encouraging the involvement of fathers in infant and child care promotion strategies, would help prevent severe wasting in these infants.