Caregiving for disabled people is a strenuous task often provided by family members, with adverse repercussions on the caregivers' health. The aim of this study was to evaluate, for the first time, the effects of a novel cognitive-based stress management technique, the Pythagorean Self-Awareness Intervention (PSAI) on the stress levels and other cognitive and psychological characteristics of non-paid caregivers of patients with motor disability. In this quasi-experimental study, 59 caregivers of first-degree relatives with motor disabilities due to chronic neurological diseases, inpatients at a Rehabilitation Center, in Athens, Greece, were assigned to an intervention (PSAI, n=28) and a control group (received unstructured consultation, n=31). Psychological, cognitive, and sleep-related measurements (Zarit Burden Interview tool, Pittsburgh Sleep Quality Index, Self-Efficacy Scale, Depression, Anxiety and Stress Scale, Symbol Digit Modalities Test, California Verbal Learning Test-II, Brief Visuospatial Memory Test-Revised) were held at baseline and after 8 weeks (at completion of PSAI) in both groups. PSAI was found to decrease caregivers' stress, depressive symptoms and anxiety and improve their sleep quality, visual memory, self-efficacy, and cognitive speed processing. Future randomized controlled studies are needed to investigate the effects of this novel intervention in larger samples of caregivers.