Extreme environments like thermal springs are of considerable value as a source of thermophilic microbes, enzymes and biotechnological substances. The hot spring of Ras-Sedr is one of the Egyptian hot springs which not discovered yet. This research was carried out to isolate and screen thermophilic microbes that have the capability to produce thermostable enzymes. The sources for microbial isolation were sediment and water samples, collected from Ras-Sedr's hot spring, Ras-Sedr, Egypt. Three different medium types were used for microbial isolation. The isolates obtained were subjected for enzymatical activity. Three different enzymes, cellulase, lipase and ά-amylase, were selected to be screened by isolated strains. For cellulase activity testing, carboxy methylcellulose (CMC) agar was used as growth medium whereas tributyrin agar medium was used for lipase enzyme, while, starch agar plates were used for amylase enzyme screening. Our results showed that sediment sample harbored higher count of microbes than the water sample. Similarly, ATCC medium recorded higher thermophilic microbial count compared to the other two media used. The isolates obtained also reported a positive activity for all enzymes tested. Therefore, these promising isolates could be a source for pharmaceuticals and industrial applications.