BACKGROUND: The number of orphans in Rakai district, Uganda is estimated to be 34,902 (OCBO, 2000) which translates into 28% of children under the age of 18 years. Young people who have been orphaned and as a result became heads of households must look after themselves and their siblings. These children are likely to be faced with several health problems and have to take crucial life decisions without parental/adult guidance. OBJECTIVES: This study was conducted in order to understand how child-headed households, Rakai district in Uganda recognize malaria, their health-seeking behavior when malaria is suspected and reasons for the type of behavior compared to the adult-headed households. METHODS: A comparative cross-sectional study was conducted in 300 households in Rakai district, Uganda, in which 8/23 (35%) of sub-counties and 150 child-headed households were included. The closest neighborhood adult-headed household to each child-headed household was selected for comparison. Individual interview was carried out with the respondents using semi-structure questionnaire. Key informant interview and focus group discussions were also conducted. RESULTS: The main findings were that the respondents in child-headed households had less knowledge on signs and symptoms of simple and severe malaria compared to adult heads of households. Respondents in child-headed households were less likely to seek health care from health facilities (OR=0.59, CI=0.36-0.97, p-value=0.028). There was no significant difference in the time lag before taking first action in the two types of households (OR=0.72, CI=0.42-1.22, p-value=0.194). The respondents in child-headed households were six times (OR=5.70,CI=2.75-11.91, p-value<0.001) more likely to use local herb for treatment of malaria than the adult heads households. Major reasons stated by the respondents for choosing where health care is sought included distance to source of health care, cheap or free treatment, availability of drugs, and quick services to patients. CONCLUSION: The respondents in child-headed households had less knowledge on signs and symptoms of simple and severe malaria and receive too little or late health care from health professionals compared to the adult heads of households probably due to lack of knowledge and money. Information Communication and Education programs should be designed and target the child-headed households and supply home packs