Arsenic is an environmental toxicant, free-radical generator, carcinogenic agent, and aging promoter. Recently, blood samples were analyzed from individuals (control- male 12, female 13; arsenic-exposed- male 16, female 14; and exposed to ≥100 μg/L As, ≥10 y) with dermatological symptoms in few affected villages in Eastern India to unravel their hematopoietic, metabolic, and antioxidant profiles. White blood cells recovered from buffy coat were used for DNA fragmentation test. Present observation suggests that significant number of individuals developed pigmentation and palmoplantar hyperkeratosis with black-brownish patch on their body and many of those developed carcinomas. Hematopoietic data show a significant increase in eosinophil and decrease in monocyte count in either sex. Though insignificant, an increase in neutrophil in female and lymphocyte count in male arsenic-exposed individuals are supported by the earlier report on sex dimorphic immune sensitization. Significant increase in serum alanine transaminase in both sexes and bilirubin only in male suggests the eventuality of hepatic disintegration. Arsenic exposure significantly decreased serum amylase in female. A significant decrease in antioxidant components like catalase, soluble thiol, and recently recognized uric acid worsened the situation by generating free radicals as observed in significant rise in malondialdehyde level, which finally increased DNA fragmentation and arsenic-associated mutagenesis and carcinogenesis. This could attribute to lowering in immune competence and related necrotic and/or apoptotic manifestations.