Background: Starting from March 2020 until December 2021, different phases of Covid-19 pandemic have been identified in Italy, with several containing/lifting measures progressively enforced by the National government. In the present study, we investigate the change in occupational risk during the subsequent pandemic phases and we propose an estimate of the incidence of the cases by economic sector, based on the analysis of insurance claims for compensation for Covid-19. Methods: Covid-19 epidemiological data available for the general population and injury claims of workers covered by the Italian public insurance system in 2020–2021 were analyzed. Monthly Incidence Rate of Covid-19 compensation claims per 100,000 workers (MIRw) was calculated by the economic sector and compared with the same indicator for general population in different pandemic periods. Results: The distribution of Covid-19 MIRw by sector significantly changed during the pandemic related to both the strength of different waves and the mitigation/lifting strategies enforced. The level of occupational fraction was very high at the beginning phase of the pandemic, decreasing to 5% at the end of 2021. Healthcare and related services were continuously hit but the incidence was significantly decreasing in 2021 in all sectors, except for postal and courier activities in transportation and storage enterprises. Conclusion The analysis of compensation claim data allowed to identify time trends for infection risk in different working sectors. The claim rates were highest for human health and social work activities but the distribution of risk among sectors was clearly influenced by the different stages of the pandemic.