Introduction Severe acquired brain injury(SABI) often results in the deterioration of physical, cognitive and emotional functions in the patient and a significant caregiver's distress syndrome, which is now amplified by the social isolation, depression and financial difficulties related to the COVID-19 pandemic. The use of web-based online-therapy has been shown to be useful to overcome caregiver's distress syndrome and further stimulate cognitive-motor recovery of SABI-patients. Our study aimed to investigate whether a systematic online Skype-therapy(OLST) may be of support in favoring global cognitive and sensory-motor recovery in SABI-patients and reducing caregiver distress. Methods Twenty-five SABI-subjects in inpatient regimen were provided with intensive OLST with the caregiver for 12 weeks in addition to standard neurorehabilitation. Each subject and caregiver was evaluated before and after the treatment by administering an ad hoc battery. Furthermore, 18 of 27 patients were provided with EEG recording in resting state. Results We found a significant reduction in caregiver's anxiety (p<0.0001) and burden(p<0.0001). Patients showed significant improvement in trunk control (p<0.0001), functional independence (p = 0.005), functional (p = 0.01) and global communication (p = 0.004), cognitive functioning (p = 0.001), and behavioral responsiveness (p = 0.0004). The training yielded a significant connectivity change within the fronto-centro-parietal areas in the delta frequency band (p<0.0001) and the centro-parieto-occipital areas in the alpha range (p = 0.004). Discussion OLST may be a useful and complementary treatment to optimize global cognitive and functional recovery in SABI-subjects and reduce caregivers' concerns in the Covid-era. OLST can foster cognitive-motor recovery potentially by favoring the plasticity-dependent functional recovery. Therefore, OLST could be proposed as a tool allowing social conversations also in the hospital setting.