OBJECTIVE: To investigate the impact of socio-economic and environmental factors on developing severe malaria in comparison with mild malaria in Yemen. METHOD: Case-control study comparing 343 children aged 6 months to 10 years diagnosed with WHO-defined severe malaria (cases) at the main children's hospital in Taiz and 445 children with mild malaria (controls) diagnosed in the health centres, which serve the areas where the cases came from. RESULTS: In univariate analysis, age <1 year, distance from health centre, delay to treatment and driving time to health centre were associated with progression from mild to severe malaria. In multivariate analysis, distance to nearest health centre >2 km was significantly associated with progression to severe disease. Environmental and vector control factors associated with protection from acquiring malaria (such as sleeping under bednets) were not associated with protection from moving from mild to severe disease. CONCLUSIONS: Innovative ways to improve access to antimalarial treatment for those living more then 2 km away from health centres such as home management of malaria, especially for infants and young children, should be explored in malaria-endemic areas of Yemen.