Study Objectives: To test whether the sleep-wake cycle disruption in patients hospitalized with traumatic brain injury (TBI) 1) is also found in patients with traumatic injuries other than TBI (nonTBI); and 2) is associated to a weaker or abnormal circadian clock signal. Methods: Forty-two non-mechanically ventilated and non-sedated patients hospitalized for moderate to severe TBI were compared to 34 non-TBI patients. They wore wrist actigraphs for 9.4±4.2 days, starting 19.3±12.6 days post-injury. Of these, 17 TBI and 14 non-TBI patients had their urine collected every hour for 25 h, starting 18.3±12.3 days post-injury. We calculated urinary 6-sulfatoxymelatonin concentration to obtain total 24 h excretion, excretion onset, offset, duration, amplitude and acrophase. Using Student’s t-tests, we compared groups on actigraphy (daytime activity ratio, nighttime total sleep time, and fragmentation index) and melatonin variables. We investigated associations between melatonin and actigraphy variables using Pearson’s correlations. Results: TBI patients had poorer daytime activity ratio (TBI: 77.5±9.4%; non-TBI: 84.6±6.9%), shorter nighttime total sleep time (TBI: 353.5±96.6 min; non-TBI: 421.2±72.2 min), and higher fragmentation index (TBI: 72.2±30.0; non-TBI: 53.5±23.6) (all p-values<0.01). A melatonin rhythm was present in both groups, and no group differences were found on melatonin variables. No associations were found between melatonin and actigraphy variables in TBI patients. Conclusion: Moderate to severe TBI patients have more serious sleep-wake disturbances than non-TBI patients hospitalized in the same environment, suggesting that the brain injury itself alters the sleepwake cycle. Despite their deregulated 24 h sleep-wake cycle, TBI patients have a normal circadian clock signal.