The management of patients with disorders of consciousness (DOC) has raised several important ethical, social, and medical issues. It is also known that families and caregivers are subjected to physical and emotional load due to their assistance activity. The aim of this observational study was to compare distress and coping strategies used among caregivers of two kinds of DOC: vegetative state (VS) and minimally conscious state (MCS). We have enrolled 80 caregivers (mean age 47.87 ± 11-28years) that were tested with self-administered measures of distress and coping to individuate which coping strategies were adopted by caregivers of DOC patients and to analyze how these have influenced the degree of distress. Data showed that the reaction to stress was different between two groups of caregivers (VS and MCS); moreover, it may vary according to the coping strategies used. Results showed the importance to develop effective coping strategies aimed to reduce psychological distress and improving caregiver's well-being.