The effect of red blood cell separation on tissue oxygenation was analyzed using a previously developed model which accounts for the particulate nature of blood at the capillary level. Results show that an empirically based RBC pattern yields the same levels of oxygenation at 20% hematocrit as an even spacing pattern. Introduction of an empirically based RBC spacing pattern during hemodilution, where capillary hematocrit is reduced by half with concomitant doubling of velocity, results in a reduction of average tissue pO2 by 23% and volume of oxygenated tissue by 28%, whereas axial delivery of oxygen along the length of the capillary was unchanged. Tissue oxygenation levels are optimized with even RBC spacing pattern but not with an empirical pattern because the tissue does not effectively use the oxygen delivered by unevenly spaced RBCs despite an equivalent time-averaged flux. Model predictions for tissue oxygenation for statistically distributed spacing under normal and hemodilution conditions show trends consistent with previously obtained results using even spacing, namely, increased axial distance and volume oxygenated, with decreased average tissue pO2. During hemodilution, the volume of tissue oxygenated above 2 mm Hg decreased to 84%, while the volume above 1 mm Hg increased to 131% relative to control. This finding suggests a redistribution of oxygen within tissue during hemodilution, causing a greater amount of tissue to be exposed, but at a lower pO2.