BACKGROUND & OBJECTIVE: Patients with brain injury are at high risk for infections. Although infection and cognitive deterioration are established for people with dementia, this has not been shown for patients with a prolonged disorder of consciousness (PDOC). This study determines whether regular Wessex Head Injury Matrix (WHIM) assessments can identify early signs of infections in patients with PDOC. METHOD: Retrospective and prospective approaches were used to assess the WHIM scores of patients with a PDOC (N = 21 in the retrospective study and 22 in the prospective study). RESULTS: The WHIM total scores decreased due to infections in 17 of the 21 cases of infection (p < 0.001) in the retrospective study and 15 (p = 0.001) of the 22 prospective cases of infection. Patients in a minimally conscious state (MCS) showed a bigger proportion of change between their baseline score and the scores taken in the pre-infection stage in both the retrospective and prospective studies when compared to patients in a vegetative state (VS). CONCLUSION: The findings suggest the importance of serial WHIM assessments throughout the period of recovery, not only to measure cognitive changes but also to highlight underlying physical changes such as infections that will impact the response to rehabilitation and recovery.