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Purpose: The aim was to analyze the differences between wheelchair basketball players with Spinal Cord Injury (SCI) and without Spinal Cord injury (Non-SCI) in psycho-physiological response and neuromuscular fatigue in a series of small-sided games (SSG). Methods: Thirteen high-level wheelchair basketball male players (age 28.8 ± 9.2 years, body mass 75.9 ± 11.3 kg) participated in four versus four SSG once a week for five consecutive weeks. Absolute and relative heart rate (HR) during SSG and muscular and respiratory perceived exertion (RPEmus and RPEres), tympanic temperature, and acceleration capacity were recorded at the end of each SSG. Results: No significant differences were observed between SCI and non-SCI players in relative HR variables in SSG series. However, the SCI group had a lower absolute HR (mean HR and peak HR) (p <.05 or p <.01, ES = 0.73–1.39) and higher perceived muscular load (RPEmusTL) (p <.01, ES = 0.75–0.82) during SSG. Regarding the evolution of the physiological response, no differences were observed between the four bouts in the SCI group. However, the Non-SCI group showed an increase in the absolute and relative variables of HR and RPEres and RPEmus (p <.05 or p <.01, ES = 0.45–1.06). On the contrary, only the SCI group showed a loss of acceleration capacity between the four series (p <.05, ES = 0.28–0.35). Conclusion: The results of this study show that there are differences between SCI and non-SCI wheelchair basketball players in their physiological response and acceleration capacity during SSG tasks. [ABSTRACT FROM AUTHOR]