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Objective: The aim was to estimate the perceived quality of life and its relationship with sociodemographic and professional factors, perception of susceptibility to COVID-19, and stress. Design: It was a longitudinal study. Subjects: Professionals, working in Italian centers for pediatric neurocognitive, speech, and psychomotor rehabilitation. Methods: Participants were interviewed online twice during the COVID-19 outbreak in Italy. The questionnaire included: (i) The measures of health-related quality of life to perform the Summary Index of Unhealthy Days, (ii) modified items from the “Standard questionnaire on risk perception of an infectious disease outbreak” and (iii) the items of the General Health Questionnaire. Results: One hundred and thirty professionals out of 130 participated in the first interview, while only 50 therapists took part in the second interview (dropout rate: 61%). The Summary Index of Unhealthy Days was 8 days at the first interview, and it decreased to 6 days at the second interview; however, the reduction was not significant (F = 3.22; p = 0.079). The multivariable analysis showed that the rehabilitation providers with moderate or severe stress level were more likely to have a negative perception of the quality of life (ORadj = 7.155; 95% CI: 2.8–18.2), and this result was confirmed at the second interview. Conclusions: Our results showed that in a severe public health emergency, the mental health and quality of life of rehabilitation professionals must be a topic of focus to enhance psychological resilience, to prevent burnout and to reduce rehabilitation errors.