We investigated the in-situ photothermal response of human red blood cells (RBCs) by combining photothermal heat generation and 3D quantitative phase imaging techniques. Gold-nanorod-coated substrates were excited using near-infrared light to generate local heat to RBCs, and response was measured by imaging 3-D refractive index tomograms of cells under various near infrared (NIR) excitation conditions. On photothermal treatment, cell morphology changed from discoid to crescent shapes, cell volume and dry mass decreased, and hemoglobin concentration increased. We also investigated the irreversible deformation of RBCs when multiple intense excitation shocks are applied. These results provide a new understanding of thermodynamic aspects of cell biology and hematology. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY