Medical comorbidities are frequent in patients with disorders of consciousness (DoC) and their impact on outcomes is under investigation. The aim of this study was to investigate patients with DoC in the acute stage and the influence of comorbidities. Patients admitted to intensive care units and neurological units with a diagnosis of coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) were investigated through the Glasgow Coma Scale (GCS), the Coma Recovery Scale – Revised (CRS-R) and the Comorbidities Coma Scale (CoCos). Forty-three patients (21 men and 22 women; mean age at admission: 60.4 ± 21.0) were included in the study. The most frequent diagnosis at admission was coma (72%) followed by VS/UWS (14%) and MCS (14%). The most frequent brain injury was subarachnoid hemorrhage (46%). At the 6-month follow-up, 19 patients had died (44%), 15 showed a full recovery of consciousness (35%), 7 were in a condition of emergence from MCS (16%), and 2 showed a persistent VS/UWS (5%). Forty-two (98%) patients showed at least one comorbidity: presence of life-support device (92.9%), anemia (76.2%), arterial hypertension (66,7%), hydrocephalus (45.3%), and respiratory infections (45.2%) were those most frequently reported. At the Multivariable Cox regression, the presence of renal disease (hazard ratio [HR] 33.37;
p
= 0.033) and malnutrition (HR 14.52;
p
= 0.001) were predictors of missed recovery of full consciousness. Although adverse outcomes are generally predicted by the severity of brain damage, the presence of medical comorbidities in an acute phase could influence outcomes and long-term prognosis.