Prolonged hospitalization in severe COVID-19 cases can lead to substantial muscle loss and functional deterioration. While rehabilitation is essential, conventional approaches face capacity challenges. Therefore, evaluating the effectiveness of robotic-assisted rehabilitation for patients with post-COVID-19 fatigue syndrome to enhance both motor function and overall recovery holds paramount significance. Our objective is to assess the effectiveness of rehabilitation in post-COVID-19 patients with upper extremity impairment through the utilization of a hand exoskeleton-based robotic system. A total of 13 participants experiencing acute or limited functional or strength impairment in an upper extremity due to COVID-19 were enrolled in the study. A structured intervention consisted of 45 min therapy sessions, conducted four times per week over a six-week period, utilizing a hand exoskeleton. The research employed standardized health assessments, motion analysis, and semi-structured interviews for pre-intervention and follow-up evaluations. Paired sample -tests were employed to statistically analyze the outcomes. The outcomes showed a reduction in overall dependence levels across participants, positive changes in various quality of life-related measurements, and an average increase of 60.4 ± 25.7% and 28.7 ± 11.2% for passive and active flexion, respectively. Our data suggest that hand exoskeleton-based robotic systems hold promise to optimize the rehabilitation outcomes following severe COVID-19. Trial registration: ID NCT06137716 at ClinicalTrials.gov.