Altered cognition or hemiparesis can occur in neurocritical but conscious patients, and recognizing pain is challenging. This study aimed to test the reliability and validity of the Critical-Care Pain Observation Tool (CPOT) in this specific group. This prospective study included ventilated, conscious patients who had certain neurologic deficits. CPOT scores were assessed before and after nociceptive (turning the patient) and non-nociceptive (measuring body temperature) procedures. The patients' self-reported pain was also recorded using a numerical rating scale (NRS). Sixty-three patients were enrolled. The intraclass correlation coefficient was r = 0.975-1.000 (p < 0.001) for turning the patient. Discriminant validation indicated that CPOT scores were significantly higher after turning the patient compared with measuring body temperature (p = 0.025). CPOT scores were positively correlated with NRS when turning the patient (r = 0.724, p < 0.001). After turning, the mean increase in CPOT score was lower in the patients with hemiparesis than in those without hemiparesis (p = 0.079), however it was significantly higher in the patients with cognitive dysfunction compared to those without cognitive dysfunction (p = 0.022). The CPOT is an appropriate instrument to assess pain in conscious patients, particularly those with cognitive dysfunction. The influence of hemiparesis on the CPOT is noteworthy.