The catfish has a high protein content and consumption level, but its utilization is not optimal. The defatting process can affect the characteristics of the protein isolate produced. This study produced protein isolates from catfish and investigated the effect of defatting solvents (n-hexane and ethanol) on physicochemical, functional, and sensory properties of catfish protein isolates (CPI). The CPI was prepared from defatted catfish flour using n-hexane (DCFh) and ethanol solvents (DCFe). The protein isolation of catfish used chemical methods to determine the solubility of protein at various pHs. The protein isolates were analysed for physicochemical, functional, and sensory properties. The results showed the highest solubility of DCFh and DCFe at pH 11 and the lowest at pH 5.5. The protein content of CPI from defatted flour with hexane (CPIh), and ethanol solvents (CPIe) were comparable, 92.02 and 93.47% db, respectively. Differences in defatting solvents affected the proximate composition (moisture; ash content), physical properties (bulk density; colour), functional (water holding capacity; foaming capacity), and sensory (dried fish taste) of CPI. Ethanol solvent could be used as an alternative for the defatting process. The CPI had good functional properties, i.e., water/oil holding capacity, emulsion capacity and stability, foaming stability, and gel strength, which could be used in food formulations and as an alternative to binders in processed meat products.