E-commerce has gained increased popularity over the last decade. To date, there is an open debate as to whether e-commerce or brick-and-mortar shopping is environmentally less sustainable, especially due to the growing mobility resources needed for e-commerce distribution. The analysis at hand compares the CO2-equivalent emissions of e-commerce and brick-and-mortar shopping of pharmaceutical products considering spatial aspects and the typical transport modal mix of consumers when doing online and offline shopping. The object of analysis is a retailer of pharmaceutical products, more precisely medicines, which offers, both, brick-and-mortar shop and online shopping possibilities. The results show that spatial aspects concerning the residential location of consumers, the vehicles used for shopping trips, the shopping basked size, and trip-chaining effects have a crucial impact on the mobility demand and CO2-equivalent emissions of the two commerce forms. In general, for rural and sub-urban areas, e-commerce results in lower CO2-equivalent emissions, while in urban areas, brick-and-mortar shopping is the favourable solution, if the consumers walk or cycle to the next pharmacy.