Objective: Sedentary behavior (SB) is associated with poor cognitive performance in the general population. Although people with schizophrenia are highly sedentary and experience marked cognitive impairments, no study has investigated the relationship between SB and cognition in people with schizophrenia. Methods: A total of 199 inpatients with schizophrenia (mean [SD] age 44.0 [9.9] years, 61.3% male, mean [SD] illness duration 23.8 [6.5]) and 60 age and sex matched controls were recruited. Sedentary behavior and physical activity (PA) were captured for 7 consecutive days with an accelerometer. Cognitive performance was assessed using the Vienna Test System, and the Grooved Pegboard Test. Multivariate regression analyses adjusting for important confounders including positive and negative symptoms, illness duration, medication, and PA were conducted. Results: The 199 patients with schizophrenia engaged in significantly more SB vs controls (581.1 (SD 127.6) vs 336.4 (SD 107.9) min per day, P < .001) and performed worse in all cognitive performance measures (all P < .001). Compared to patients with high levels of SB (n = 89), patients with lower levels of SB (n = 110) had significantly (P < .05) better motor reaction time and cognitive processing. In the fully adjusted multivariate analysis, SB was independently associated with slower motor reaction time (beta = .162, P < .05) but not other cognitive outcomes. Lower levels of PA were independently associated with worse attention and processing speed (P <.05). Conclusion: Our data suggest that higher levels of sedentary behavior and physical inactivity are independently associated with worse performance across several cognitive domains. Interventions targeting reductions in SB and increased PA should be explored.