In Nogales, Sonora, Mexico, some neighborhoods, or colonias, have intermittent delivery of water through pipes from the city of Nogales’s municipal water-delivery system while other areas lack piped water and rely on water delivered by truck or pipas. This research examined how lifestyles, water quality, and potential disease response, such as diarrhea, differs seasonally from a colonia with access to piped water as opposed to one using alternative water-delivery systems. Water samples were collected from taps or spigots at homes in two Nogales colonias. One colonia reflected high socio-environmental conditions where residents are supplied with municipal piped water (Colonia Lomas de Fatima); the second colonia reflected low socio-environmental conditions, lacking access to piped water and served by pipas (Colonia Luis Donaldo Colosio). A survey was developed and implemented to characterize perceptions of water quality, health impacts, and quality of life. Water samples were analyzed for microbial and inorganic water-quality parameters known to impact human health including, Escherichia coli (E. coli), total coliform bacteria, arsenic, and lead. A total of 21 households agreed to participate in the study (14 in Colosio and 7 in Fatima). In both colonias metal concentrations from water samples were all well below the United States Environmental Protection Agency’s (US EPA’s) maximum contaminant levels. E. coli concentrations exceeded the US EPA’s drinking-water standard in Colosio but not Fatima. Total coliform bacteria were present in over 50 % of households in both colonias. Microbial contamination was significantly higher in the summer than in the winter in both colonias. Resulting analysis suggests that residents in colonias without piped water are at a greater risk of gastrointestinal illness from consumption of compromised drinking water. Our survey corroborated reports of gastrointestinal illness in the summer months but not in the winter. Chloride was found to be significantly greater in Colosio (median 29.2 mg/L) although still below the US EPA’s maximum contaminant levels of 250 mg/L. Ongoing binational collaboration can promote mechanisms to improve water quality in cities located in the US–Mexico border.