Polymorphisms of the haptoglobin (HP) gene and deletions in alpha-globin gene (alpha-thalassaemia) are common in malaria-endemic Africa. The same region also has high incidence rates for childhood acute seizures. The haptoglobin HP2-2 genotype has been associated with idiopathic generalized epilepsies and altered iron metabolism in children with alpha-thalassaemia can potentially interfere with neurotransmission and increase the risk of seizures. We investigated the hypothesis that the HP2-2 genotype and the common African alpha-globin gene deletions are associated with the increased risk of seizures. 288 children aged 3-156 months admitted with acute seizures to Kilifi District Hospital (Kenya), were matched for ethnicity to an equal number of community controls. The proportion of cases (72/288 [25.0%]) and controls (80/288 [27.8%]) with HP2-2 genotype was similar, p=0.499. The allele frequency of HP2 gene in cases (49.3%) and controls (48.6%) was also similar, p=0.814. Similarly, we found no significant difference between the proportion of cases (177/267 [66.3%]) and controls (186/267 [69.7%]) with deletions in alpha-globin gene (p=0.403). Among cases, HP2-2 polymorphism and deletions in alpha-globin gene were neither associated with changes in the type, number or duration of seizures nor did they affect outcome. We conclude that the HP2-2 polymorphism and deletions in alpha-globin gene are not risk factors for acute seizures in children. Future studies should examine other susceptibility genes.