We previously reported the presence in the membrane erythrocyte of a TSH receptor (TSHR), a G-protein coupled receptor, which responds to TSH with increased cAMP level. Since there is evidence for a role of G protein receptors as oxygen sensor(s) implicated in cell volume regulation, we hypothesized that erythrocyte TSHR, by TSH stimulation, could modify the erythrocyte volume and the oxygenation state of erythrocytes. We determined the effect of TSH on the gas analysis in 35 thyroidectomized patients for stage I differentiated thyroid cancer enrolled for recombinant human thyroid-stimulating hormone (rhTSH) test during chronic treatment with synthetic l-thyroxine. Moreover, we explored the influence of TSH on the shape of erythrocytes. Venous blood-gas analysis before and after TSH were determined with a pH/blood gas electrolyte and 682 CO-Oxymeter. In a subgroup of subjects (n=10), the isolated red blood cells (RBC) were analyzed by flow cytometry for morphological changes. After TSH stimulation, we found a significant decrease in PCO₂ (P<0.001), an increase in pH (P<0.01) and an increase of % O₂-Hb (P<0.05) and pO₂ (P<0.05). By flow cytometry, the erythrocytes after TSH showed a significant enrichment on the mean number in the selected region R1 corresponding to bigger volumes (P<0.05, n=10). Finally, by contrast phase microscopy, when the cell area was measured, a mean increased volume was observed in erythrocytes after TSH compared to the basal before TSH (P<0.05). In conclusion, our results indicate that acute stimulation of TSH by rhTSH modifies the oxygenation state and volume of erythrocyte.