BACKGROUND: Low hemoglobin (Hb) is associated with poor general health and adverse outcomes in a wide range of diseases. However, a link between Hb levels and the risk of infection among healthy individuals has yet to be investigated. STUDY DESIGN AND METHODS: Using data from the Scandinavian Donations and Transfusions database, 497,390 donors were followed after 5,458,499 donations in health registers. With 1,339,362 person-years of follow-up, Andersen-Gill Cox regression was used to study the association of Hb levels below deferral thresholds, very low Hb levels (in the lowest 0.1 percentile), and declining Hb levels with the risk of infection as measured by hospital or outpatient contact for infection and filling of prescription for antimicrobials, respectively, within 3 months of donation. Analyses were stratified by sex, menopausal status, and frequency of donation. RESULTS: Hb levels below deferral thresholds were not associated with a risk of hospital contact for infection among premenopausal women (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95-1.14), postmenopausal women (HR, 0.77; 95% CI, 0.54-1.11), or men (HR, 0.97; 95% CI, 0.81-1.16), nor was there any association with hospital contact for very low Hb levels or patterns of declining Hb levels. However, subthreshold Hb levels were associated with a reduced risk of antimicrobial prescriptions among premenopausal women (HR, 0.92; 95% CI, 0.91-0.93), postmenopausal women (HR, 0.93; 95% CI, 0.89-0.97), and men (HR, 0.91; 95% CI, 0.88-0.94). CONCLUSIONS: Neither Hb levels below deferral thresholds nor very low or declining Hb levels were associated with an increased risk of infection. This is reassuring, because blood donation can lead to lower Hb levels.