The major histocompatibility complex is linked to white blood cell (WBC) and lymphocyte counts in subjects unselected for HFE genotypes. We compared age, sex, body mass index, total WBC and subtypes (neutrophils, lymphocytes, monocytes, eosinophils, basophils) (Beckman Coulter® Gen-S), transferrin saturation, and serum ferritin of HFE p.C282Y and wild-type (p.C282Y, p.H63D negative) homozygotes without acquired conditions that influence WBC counts. We performed regressions on WBC and subtypes. There were 161 p.C282Y homozygotes (45.3% men) and 221 wild-type homozygotes (40.3% men). Mean WBC of men and women and between HFE genotypes were similar. Mean lymphocytes were higher in male p.C282Y homozygotes: 1.6 × 109/L [95% confidence interval: 1.5,1.7] vs. 1.4 [1.3,1.5], p = 0.0002. Mean lymphocytes and basophils were higher in female p.C282Y homozygotes: 1.6 [1.5,1.7] vs. 1.4 [1.3,1.5], p = 0.0002; and 0.065 [0.059,0.071] vs. 0.052 [0.051,0.054], p = 0.0001, respectively. Transferrin saturation was associated with neutrophils (negative; p = 0.0163). Age was associated with lymphocytes (negative; p = 0.0003) and monocytes (positive; p < 0.0001). Regressions on lymphocytes and basophils revealed positive associations with p.C282Y homozygosity (p = 0.0043 and 0.0003, respectively). There were significant positive associations of neutrophils, lymphocytes, monocytes, and eosinophils. We conclude that HFE p.C282Y homozygosity is significantly associated with lymphocyte and basophil counts.