**Background:** Non-pharmaceutical interventions (NPIs) have been widely used to control COVID-19, but their effectiveness has been understudied in Gulf states, including Saudi Arabia, which has a distinct demographic profile (38% foreign nationals) and hosts large religious pilgrimages. The first COVID-19 case in Saudi Arabia was reported on March 2, 2020, and by October 10, 2020, over 300,000 confirmed cases and 4,923 deaths had been reported. This study aimed to estimate the association between NPI implementation and changes in SARS-CoV-2 transmission across Saudi Arabian regions during the first pandemic wave.
**Methods:** The authors obtained region-level daily incident case and death data from the Saudi Ministry of Health COVID-19 dashboard (March 2 to October 10, 2020). NPI timelines were compiled from news and government sources. A spatial SEIR-type model was fitted to observed data, with transmission dynamics modeled at the administrative region level. Population mobility fluxes between regions were obtained from Facebook Data for Good. The model estimated region-specific parameters for epidemic seeding, the basic reproduction number (R0), and NPI effectiveness. NPIs were grouped into 7 categories based on timing: 1) Isolate and Test with School Closure, 2) Curfew part one, 3) Curfew part two, 4) Lockdown (5-day 24-hour curfew, May 23–27), 5) Phase I relaxation (May 28–30), 6) Phase II relaxation (May 31–June 20), and 7) Phase III relaxation (from June 21 onward, subdivided into two periods). Inference used a Poisson likelihood on weekly confirmed cases and a square-root normal likelihood on deaths.
**Key Results:** Modeled epidemic trajectories were well calibrated, with 91% (Al Jawf) to 99.5% (Asir) coverage for incident cases and 92% to 100% coverage for incident deaths across regions. Region-level estimates of the basic reproduction number ranged from 1.7 (Al Jawf) to 2.3 (Hail). The Isolate and Test with School Closure NPI was associated with transmission reductions between 25% (Makkah, IQR CrIs: 9%–35%) and 41% (Asir, IQR CrIs: 22%–60%), with a mean effect of 36% across regions, though 95% CrIs ranged from 1% to 73%. Curfew part one was associated with reductions from 22% (Makkah, IQR CrIs: 9%–34%) to 70% (Najran, IQR CrIs: 64%–84%), and Curfew part two from 30% (Najran, IQR CrIs: 9%–47%) to 65% (Al Madinah, IQR CrIs: 54%–81%). Lockdown was associated with 50%–60% reductions across all regions (IQR CrIs: 26%–81%). During relaxation phases, Phase I showed 35%–40% reductions (except Makkah at 55%), Phase II showed 20%–50% reductions, and Phase III showed 47%–68% reductions in the first half and 48%–69% in the second half. Transmission reduction weakened during the second half of Phase III in 7 of 13 regions (mean transmission increase of 5%). The effective reproduction number dropped below 1 in 11 of 13 regions during NPIs but rose above 1 during early relaxation phases, returning near 1 by the end of the study period.
**Clinical Implications:** This study provides some of the first empirical estimates of NPI effectiveness for Saudi Arabia and the Gulf region. The findings suggest that combinations of NPIs—particularly early isolation and testing with school closures, curfews, and lockdowns—were associated with substantial reductions in SARS-CoV-2 transmission, though with considerable uncertainty. The increase in transmission during later relaxation phases highlights the challenge of maintaining control as restrictions are lifted. These estimates may serve as a baseline for planning NPI scenarios in the context of emerging variants and vaccination, though the authors caution that inferences may not apply to future periods given changes in vaccination coverage, variant emergence, and the resumption of religious pilgrimages.