We use regional air quality modeling to evaluate the impact of model resolution on uncertainty associated with the human health benefits resulting from proposed air quality regulations. Using a regional photochemical model (CAMx), we ran a modeling episode with meteorological inputs representing conditions as they occurred during August through September 2006, and two emissions inventories (a 2006 base case and a 2018 proposed control scenario, both for Houston, Texas) at 36, 12, 4 and 2 km resolution. The base case model performance was evaluated for each resolution against daily maximum 8-h averaged ozone measured at monitoring stations. Results from each resolution were more similar to each other than they were to measured values. Population-weighted ozone concentrations were calculated for each resolution and applied to concentration response functions (with 95% confidence intervals) to estimate the health impacts of modeled ozone reduction from the base case to the control scenario. We found that estimated avoided mortalities were not significantly different between 2, 4 and 12 km resolution runs, but 36 km resolution may over-predict some potential health impacts. Given the cost/benefit analysis requirements of the Clean Air Act, the uncertainty associated with human health impacts and therefore the results reported in this study, we conclude that health impacts calculated from population weighted ozone concentrations obtained using regional photochemical models at 36 km resolution fall within the range of values obtained using fine (12 km or finer) resolution modeling. However, in some cases, 36 km resolution may not be fine enough to statistically replicate the results achieved using 2 and 4 km resolution. On average, when modeling at 36 km resolution, 7 deaths per ozone month were avoided because of ozone reductions resulting from the proposed emissions reductions (95% confidence interval was 2–9). When modeling at 2, 4 or 12 km finer scale resolution, on average 5 deaths were avoided due to the same reductions (95% confidence interval was 2–7). Initial results for this specific region show that modeling at a resolution finer than 12 km is unlikely to improve uncertainty in benefits analysis. We suggest that 12 km resolution may be appropriate for uncertainty analyses in areas with similar chemistry, but that resolution requirements should be assessed on a case-by-case basis and revised as confidence intervals for concentration-response functions are updated.