PURPOSE: Unilateral cerebral palsy (UCP) represents about 30–40% of overall cerebral palsy diagnoses. Upper limb impairment has a significant negative impact on activities of daily living (ADL), and recent studies have shown that the use of virtual reality (VR) can increase motivation and promote an improvement in ADL. This preliminary study was aimed at exploring the acceptability and usability of a VR rehabilitation treatment, using the VITAMIN Platform, for children with UCP. A secondary goal of the study was to compare the results of usual standardized clinical scales and questionnaires with kinematic results as well as with the quantitative measures acquired by the VITAMIN platform in each exercise of the rehabilitation sessions. METHODS: Six children with UCP (aged 7–15) were recruited for a preliminary investigation in using a non-immersive VR system. The treatment was composed of 10 weekly sessions of 45 minutes. Each child played five types of exergames, using the impaired upper limb to hit virtual objects projected on a wide screen. Standardized clinical scales, kinematic analysis, and questionnaires were used to extensively assess upper limb function before and at the end of treatment. Five typically-developing children provided a reference for the instrumented kinematic assessment. RESULTS: At the end of the treatment, Melbourne Assessment 2 (MA2) scores increased for all the participants (mean increase in range of movement (ROM) + 19.1%, accuracy + 4.6%, dexterity + 13.1%, fluency + 10.3%). Shoulder flexion-extension ROM also improved (mean increase + 210.5°), and according to the kinematic analysis, shoulder movements became more similar to reference profiles. These results were confirmed by a general improvement in performing ADL, assessed by the ABILHAND-Kids questionnaire. Finally, a general agreement among the different measures and indexes emerged from the acquired data. CONCLUSION: The results show that VR treatment with the VITAMIN platform could be engaging and functional for rehabilitation of children with UCP. The good agreement among the qualitative and quantitative measures and indexes confirms the potential of such novel treatment. However, due to the limited sample size and small number of sessions, further and larger investigations are required to evaluate the effectiveness and to generalize the results.