In early 2006, coinciding with heavy rains, Botswana health facilities reported increases in diarrhea, mortality, and acute malnutrition among young children. Data on diarrhea, human immunodeficiency virus, feeding, mortality, and water/sanitation were collected by random cluster survey. Anthropometric data were measured and drinking water samples were tested. Of 537 surveyed children less than five years of age, one-third experienced ≥ 1 episode of diarrhea. Prevalence of acute malnutrition was 7.9%, and the mortality rate for children less than five years of age was 2.6/10,000/day during the outbreak. Significant risk factors for diarrhea included an age less than two years; breastfeeding was protective. Diarrhea lasting for more than 14 days and failure to thrive were risk factors for acute malnutrition. Prevalence of acute malnutrition was higher than previously documented and the mortality rate in children less than five years of age during the outbreak was above the international threshold for emergency action with an estimated 547 excess deaths. This survey highlights the need for safe infant feeding and effective treatment of malnutrition and diarrhea in young children.