Blood viscosity may affect the mechanisms of stroke and early neurological deterioration (END). We aimed to investigate the relationship between blood viscosity, stroke mechanisms, and END in patients with middle cerebral artery (MCA) infarction. Patients with symptomatic MCA atherosclerosis (≥ 50% stenosis) were recruited. Blood viscosity was compared across patients with different mechanisms of symptomatic MCA disease: in situ thrombo-occlusion (sMCA-IST), artery-to-artery embolism (sMCA-AAE), and local branch occlusion (sMCA-LBO). END was defined as four points increase in the National Institutes of Health Stroke Scale score from baseline during the first week. The association between blood viscosity and END was also evaluated. A total of 360 patients (76 with sMCA-IST, 216 with sMCA-AAE, and 68 with sMCA-LBO) were investigated. Blood viscosity was highest in patients with sMCA-IST, followed by sMCA-AAE and sMCA-LBO (P< 0.001). Blood viscosity was associated with END in patients with MCA disease. Low shear viscosity was associated with END in patients with sMCA- LBO (adjusted odds ratio, aOR 1.524; 95% confidence interval, CI 1.035–2.246), sMCA- IST (aOR 1.365; 95% CI 1.013–1.839), and sMCA- AAE (aOR 1.285; 95% CI 1.010–1.634). Blood viscosity was related to END in patients with stroke caused by MCA disease.