Scientists have probed into the diverse populations in the ecosystem searching for feasible solutions to the rising existence of antibiotic resistance mechanisms that are threatening the ability to treat infectious diseases. Marine sponges are recognized as the richest sources of new marine natural products and have been shown to contain associated bacteria and fungi which produce compounds exhibiting microbial activity. In the study, fungal isolates obtained from an unidentified marine sponge were tested against Bacillus subtilis, Micrococcus luteus, Rhizopus oryzae and Saccharomyces cerevisiae. Three strips of the sponge were placed in three test tubes containing yeast peptone glucose (YPG) broth and were incubated for 7 days at 37°C. The three samples were each diluted in ten test tubes. One and a half mL was pipetted to YPG agar plates from test tubes 8 to 10 for every sample. Four fungal isolates were obtained from the three samples and purified through streak plate method. These were then assayed through cross streak method using modified YPG agar as the medium. Of the four isolates tested against the four test organisms, only one isolate exhibited activity against Rhizopus oryzae and none against the other organisms. The isolate was further tested through disc diffusion technique. Analysis of zones of inhibition proved that antifungal activity was exhibited. This provides another source of inhibitory compound. Further tests are recommended to validate results.