Objective: Carpal tunnel syndrome (CTS) is the most common focal nerve injury. People with CTS may show alterations in central processing of nociceptive information. It remains unclear whether the central sensitization inventory (CSI) is capable of detecting such altered central pain processing. Methods: Thirty healthy volunteers were matched with 30 people with unilateral CTS from the orthopaedic waitlist. Changes to central pain processing were established through psychophysical sensory testing (bilateral pressure pain thresholds (PPT), conditioned pain modulation, temporal summation) and pain distribution on body charts. Patients also completed pain severity and function questionnaires, psychological questionnaires and the CSI. Results: Compared to healthy volunteers, patients with CTS have lower PPTs over the carpal tunnel bilaterally (t = −4.06, p < 0.0001 ipsilateral and t = −4.58, p < 0.0001 contralateral) and reduced conditioned pain modulation efficacy (t = −7.31, p <0.0001) but no differences in temporal summation (t = 0.52, p = 0.60). The CSI was not associated with psychophysical measures or pain distributions indicative of altered central pain processing. However, there was a correlation of the CSI with the Beck Depression Inventory (r = 0.426; p = 0.019). Conclusion: Patients with CTS show signs of altered central pain mechanisms. The CSI seems unsuitable to detect changes in central pain processing but is rather associated with psychological factors in people with focal nerve injuries.