Columnaris disease is one of the most important bacterial diseases affecting Channel Catfish Ictalurus punctatus commercially grown in the USA. This disease can greatly diminish the profitability of aquaculture operations by large-scale mortality events, particularly in the fingerling production phase. Three experiments were conducted to evaluate the susceptibility of Channel Catfish fingerlings to columnaris disease when they were preexposed to copper sulfate (CuSO4). In experiment 1, fish were exposed for 24 h to 0, 1, 2, or 4 mg/L CuSO4 and were challenged immediately with Flavobacterium columnare, the etiological agent of columnaris disease. The resulting survival data indicated that fish preexposed to CuSO4 and then challenged exhibited significantly lower survival than did fish not exposed and then challenged. Experiment 2 was designed as above, except after the 24-h static exposure to CuSO4, fish were subjected to an additional 24 h in flow-through water prior to the challenge with F. columnare. In contrast to experiment 1, fish preexposed to CuSO4 and allowed an additional 24 h in flow-through water had a significantly higher survival rate than fish not exposed and then challenged. Experiment 3 evaluated the longevity of resistance to columnaris disease afforded by preexposure to CuSO4; in this experiment the remaining fish from experiment 2 were challenged 9 d after exposure to CuSO4. The increased survival rate of fish preexposed to CuSO4 was still significantly different, indicating the incurred resistance to F. columnare lasts for at least a week after exposure to CuSO4.