An experiment was performed to evaluate the efficacy of potassium permanganate (KMnO4) as a prophylactic and therapeutic treatment of an experimental subacute infection of Flavobacterium columnare in channel catfish, Ictalurus punctatus. Fish were cutaneously abraded and divided into five treatment groups: (i) challenged by waterborne exposure to F. columnare and not treated with KMnO4 (positive control), (ii) challenged and simultaneously treated with KMnO4, (iii) challenged and treated with KMnO4 at 1, 6 and 9 days post-challenge, (iv) not challenged and treated with KMnO4 at 1, 6 and 9 days post-challenge (first negative control) and (v) not challenged and not treated (second negative control). The dosing of KMnO4 was 2.0 mg L−1 above the potassium permanganate demand for 2 h duration. The survival of the group challenged and simultaneously treated with KMnO4 (99%) was significantly higher than the positive control (78%) and was not significantly different from the negative control groups. The challenged fish treated with KMnO4 post-challenge had 7% higher survival than the positive control (85% compared with 78%), but that difference was not statistically significant. The results demonstrate that KMnO4 has a clear prophylactic value but probably a marginal therapeutic value once the infection has established.