Hematological parameters of birds and mammals seem to respond to environmental requirements, such as hypoxia at high altitude and the energetic demands of locomotion and flight. In this work we hypothesize that lung capillary hematocrit and red blood size may be influenced by the energetic requirements of flight. Also, we propose that hematological parameters should vary together with the morphological parameters that determine oxygen diffusion capacity. We analyzed the red blood cell size and the local characteristics of the pulmonary capillary hematocrit correlating these with the pulmonary factors that determines the oxygen diffusion capacity. We deal with seven species, non-flying and flying birds and mammals, with different energetic requirements. The capillary hematocrit was not different in each taxon, but the red blood cell size was smaller in flying mammals and birds than non-flying ones. Correlation of erythrocyte size with the diffusing characteristics of the lungs produced a non-phylogenetic clustering with a group constituting by the bats Tadarida brasiliensis y Myotis chiloensis, and the bird Z. auriculata; revealing similar functional response in unrelated species. Finally, in mammals, a negative correlation between the red blood cell size and the mass-specific oxygen diffusion capacity was obtained. These results suggest that the direction of the hematological and pulmonary adjustments is governed mainly by the requirements of flight independent of phylogenetic origin of the species studied