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Abstract ObjectivesThe advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro‐gas exchanger integrated with microfluidics to studyRBCadhesion under hypoxic flow conditions mimicking postcapillary venules. MethodsWe simulated a range of physiological conditions and exploredRBCadhesion to endothelial or subendothelial components (FNorLN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation ofRBCadhesion was performed on 35 subjects with homozygousSCD. ResultsSignificant heterogeneity inRBCadherence response to hypoxia was seen amongSCDpatients.RBCs from a HEA population showed a significantly greater increase in adhesion compared toRBCs from a HNA population, for bothFNandLN. ConclusionsThe approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification ofRBCadhesion in a cost‐efficient and patient‐specific manner. We identified a unique patient population in whichRBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.