Recently in Atlantic Canada, there has been increased concern associated with potato farming due to an increase in the frequency and magnitude of fish kills downstream of agricultural cultivation activities following major storm events. Over a period of three years (1999–2001), we monitored the population structure and physiological performance of slimy sculpin (Cottus cognatus) within the Little River, located in an intensive potato cultivation region of northwestern New Brunswick. The slimy sculpin, a small-bodied benthic fish, was considered suitable for monitoring due to its natural abundance throughout the system, limited mobility, lack of commercial fishing pressures, and easily measured life history characteristics. Rather than focus on particular agricultural stressors, an effects-based assessment of the fish in the system was conducted to determine whether there were observable and persistent responses of sculpin in the agricultural region. We found that the local population structure at agricultural sites consisted of fewer young-of-the-year sculpin in 2 of 3 fall collections. In comparison with forested reaches, adult sculpin were larger but with smaller gonads, and females had smaller livers, gonads, and fewer and smaller eggs. These biological responses were reduced in the fall of the third year following drier conditions than the previous two years. The effects-based approach successfully demonstrated biological impacts on sculpin both temporally and spatially and therefore the species' potential for studying non-point source impacts in environmental monitoring.