This study examined the changes in resting hematological variables in ultra-endurance runners throughout a multi-stage ultra-marathon competition, and compared athletes that completed all stages with those that failed to complete at least one stage within the cut-off time of competition. 19 ultra-endurance runners competing in a 230 km multi-stage ultra-marathon, conducted over 5 consecutive days in hot ambient conditions (32–40°C Tmax), volunteered to participate in the study. Each day, whole blood samples were collected prior to stage commencement and analyzed for full cell counts by Coulter counter. Linear increases were observed for leukocytes, monocytes and lymphocytes; with increases until Stage 3 and a decrease thereafter. Granulocytes showed a cubic growth exponent, indicating decrements to baseline after the significant increments until Stage 3. Hemoglobin and hematocrit showed linear decrements throughout the multi-stage ultra-marathon. No changes in erythrocytes and platelets were observed throughout the multi-stage ultra-marathon. Granulocytes, erythrocytes, hemoglobin and hematocrit changes along the multi-stage ultra-marathon differed in runners that completed all stages compared to those who failed to complete at least one stage within the cut-off time. Multi-stage ultra-marathon in the heat has a large impact on hematological responses of ultra-endurance runners associated with altered performance.