Single interventions for helminthic infections and micronutrient deficiencies are effective, but it is not clear whether combined interventions will provide equal, additive or synergistic effects to improve children's health. The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children. A double-blind, randomized, placebo-controlled trial in 11 rural South African primary school randomly allocated 579 children aged between 8 and 10 years into six study groups, half of whom received antihelminthic treatment at baseline. The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits, either unfortified or fortified with vitamin A and iron or with vitamin A only, given daily for 16 weeks. The outcome measures were anthropometric, micronutrient and parasite status, and scholastic and cognitive test scores. There was a significant treatment effect of vitamin A on serum retinol (p < 0.01), and the suggestion of an additive effect between vitamin A fortification and de-worming. Fortified biscuits improved micronutrient status in rural primary school children; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection. The burden of micronutrient deficiency (anaemia, iron and vitamin A) and stunting in this study population was low and, coupled with the restricted duration of the intervention (16 weeks), might have limited the impact of the interventions.