Anemia is a significant public health problem among children worldwide. The etiology of anemia is multifactorial but iron deficiency (ID) is the most common cause of anemia in low- and middle-income countries. ID and anemia in infancy can impair growth and cognitive development. The aim of this study was to determine the prevalence and predictors of anemia among six-week-old infants in Kwale County, Kenya. This cross-sectional study included 424 mother-infant pairs. Structured questionnaires were administered to the mothers to obtain information on socio-demographic variables, maternal characteristics and birth information. Anthropometric data was collected for each child. A heel prick was done to measure hemoglobin and zinc protoporphyrin concentration levels. Chi-square test, bivariate and multivariate regression analyses were done to determine factors associated with anemia. The prevalence of ID, anemia and IDA was 60.4% (95%CI: 55.9-65.2), 21.0% (95%CI: 17.5-25.2) and 15.8% (95%CI: 12.7-19.7) respectively. Bivariate analysis showed that the risk of anemia was significantly higher among male infants (odds ratio (OR) = 2.20 (95%CI: 1.33-3.63), p = 0.002), iron deficient infants (OR = 2.35 (95%CI: 1.39-3.99), p = 0.001) and infants from Msambweni Sub-County (OR = 2.80 (95%CI: 1.40-4.62), p<0.001). Multivariate analysis revealed that odds of anemia were significantly higher in infants born to mothers who did not use iron supplements during pregnancy (adjusted odds ratio (aOR) = 74.01 (95%CI: 2.45-2238.21), p = 0.013 and significantly lower in infants born to mothers with parity ≥ 4 (aOR = 0.05 ((95%CI: 0.00-0.77), p = 0.024). In six-week-old infants in rural Kenya, anemia prevalence was 21.0% with ID accounting for 75.3% of anemia cases. Given the physical and cognitive impairments associated with ID and anemia in early infancy, it may be prudent to re-evaluate the current Kenyan pediatric protocols to include anemia screening and potential treatment of infants less than 6-months of age.