Patients with carpal tunnel syndrome (CTS) often show bilaterally increased pain sensitivity and widespread symptoms. We evaluated the influence of centrally mediated symptoms on functional outcomes of carpal tunnel release (CTR). A total of 120 patients with surgically treated CTS were enrolled. Centrally mediated symptoms were preoperatively measured by administering a self-reported central sensitization inventory (CSI) questionnaire and peripheral sensitization was measured by assessing patient’s pressure pain thresholds (PPT) in the forearm. Boston Carpal Tunnel Questionnaires (BCTQ) were assessed preoperatively and postoperatively at 3 and 12 months. CSI scores slightly correlated with symptom duration and moderately correlated with preoperative BCTQ scores, while PPT slightly correlated with the BCTQ scores. At 3 months, BCTQ symptom and function scores moderately correlated with lower PPTs and higher CSI scores. At 12 months, only severe electrophysiological grade was associated with BCTQ function scores. Multivariable analysis revealed that preoperative PPT, CSI, and female gender were associated with BCTQ scores at 3 months; these factors failed to be associated for 12-month outcomes. Centrally mediated symptoms measured by CSI and peripheral sensitization measured by PPTs correlated with symptom severity and duration. They were associated with poorer functional outcomes after CTR up to 3 months. However, they did not show persistent effects in the long term.