We conducted a cross-sectional study to identify the socio-economic and environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication, adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe malaria. Using stepwise logistic regression with all the variables inserted in the model yielded similar results. These findings suggest specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria.