Introduction Evidence for the effect of neighbourhood food environment (NFE) exposures on diet in the UK is mixed, potentially due to exposure misclassification. This study used the first national COVID-19 lockdown in England as an opportunity to isolate the independent effects of the NFE exposure on food and drink purchasing, and assessed whether these varied by region. Methods Transaction-level purchasing data for food and drink items for at-home (1,221 households) and out-of-home consumption (171 individuals) were available from the GB Kantar Fast Moving Consumer Goods Panel for London and the North of England. The study period included 23rd March to 10th May 2020 ('lockdown'), and the same period in 2019 for comparison. NFE exposures included food outlet density and proximity, and NFE composition within a 1 km network buffer around the home. Associations were estimated for both years separately, adjusted for individual and household characteristics, population density and area deprivation. Interaction terms between region and exposures were explored. Results There were no consistent patterns of association between NFE exposures and food and drink purchasing in either time period. In 2019, there was some evidence for a 1.4% decrease in energy purchased from ultra-processed foods for each additional 500 m in the distance to the nearest OOH outlet (IR 0.986, 95% CI 0.977 to 0.995, p = 0.020). In 2020, there was some evidence for a 1.8% reduction in total take-home energy for each additional chain supermarket per km2 in the neighbourhood (IR 0.982, 95% CI 0.969, 0.995, p = 0.045). Region-specific effects were observed in 2019 only. Discussion Findings suggest that the differences in exposure to the NFE may not explain differences in the patterns or healthiness of grocery purchasing. Observed pre-pandemic region-specific effects allude to the importance of geographical context when designing research and policy. Future research may assess associations for those who relied on their NFE during lockdown.