BackgroundIn COVID-19 management, a variety of pharmaceutical interventions (PI) and non- pharmaceutical interventions (NPI) were adopted to limit the spread of the disease and its associated deaths. We aimed to evaluate the impact of PI and NPI on risks of COVID-19 transmission and deaths.MethodWe collected aggregate data from March 2nd, 2020, to December 1, 2022 from the Tunisian Ministry of Health's website and OurWorldInData.org site. NPI Periods (NPIP: March 2020 to March 2021) and PI Periods (PIP) were distributed to NPIP1, 2, 3 and 4 and to PIP1, 2, 3 and 4, respectively. We calculated the Relative Risks (RR) and 95% Confidence Intervals (CI) by comparing the subsequent period with previous one.ResultsThe risk of SARS-CoV-2 transmission increased progressively from the zero cases period (NPIP2) to the mitigate strategy period (NPIP3) (RR = 14.0; 95% CI: 12.4–15.8) and to the stop-and-go epidemic control period (NPIP4) (RR = 23.1 (95% CI: 22.4–23.9). It was stabilized in the targeted vaccination period (PIP1) (RR = 1.08, 95% CI: 1.07–1.08) and reduced during the mass vaccination period (PIP2) (RR: 0.50, 95% CI: 0.50–0.51). SARS-CoV-2 transmission, increased during PIP3 concomitant with the Omicron wave (RR = 2.65, 95% CI: 2.64–2.67). It remained at a low level in PIP4 (RR = 0.18; 95% CI: 0.18–0.18).Compared to NPIP2, NPIP3 and NPIP4 were associated with a higher risk of COVID-19 mortality (RR = 3.337; 95% CI: 1.797–6.195) and (RR = 72.63 (95% CI: 54.01–97.68), respectively. Since the start of the immunization program, the risk of COVID-19 death has consistently decreased. In comparison to each previous period, the risk transitioned in PIP1 to RR = 0.91; 95% CI: 0.88–0.93, then to RR = 0.85; 95% CI: 0.83–0.88 in PIP2, to RR = 0.47; 95% CI: 0.45–0.50 in PIP3, and to RR = 0.19; 95% CI: 0.18–0.24 during PIP4.ConclusionIn terms of lowering the risk of transmission and mortality, the NP strategy at the beginning of the epidemic outperformed the IP strategy during the outbreak.