Seventy-two catfishes weighing between 200 and 250g (and distributed into 3 groups) were subjected to bath medication with ciprofloxacin at 25mg/litre of water. Medicated water of each group (24 catfishes/group) had the same pH of 6.6, after adjustment using sodium carbonate, but different levels of calcium hardness .Group A water had 12.5mg/litre of calcium hardness, while for groups B and C, the levels of the calcium hardness were adjusted to 212.5mg/litre and 412.5mg/litre respectively using calcium chloride. Samples (blood, liver, kidney and muscle) were taken from two randomly selected fishes in each group within 8 hours of exposure to ciprofloxacin. These were taken at 0 h, 0.5h, 1 h, 2 h, 4 h, and 8 h and were preserved at-0.5°C, prior to processing and drug extraction. Ciprofloxacin level was quantified by ELISA. The sera area under the curve (AUC) values of groups A, B and C were 17,938.13 µg.hr./L, 18,883.75 µg.hr./L and 12,273.75 µg.hr./L respectively, showing that at the highest concentration of calcium ions in medicated water (as seen in group c) level of the absorption .of ciprofloxacin will be reduced , hence reduced bioavailability There was also a direct linear relationship between the AUC values for tissue and the level of calcium hardness of water. This study therefore suggests a need to strongly consider the influence of core chemical parameters of fish culture water such as hardness, alkalinity and pH, as these can reduce efficacy or increase toxicity of drugs that are administered to fish by bath method.