Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persi-sting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment. Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of wor-king age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the asses-sment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.