Columnaris disease is a serious disease in warm water fish. It is caused by Flavobacterium columnare, a Gram-negative bacterium. In this work, fucoidan was tested for its efficacy in decreasing the mortalities caused by Columnaris disease in Nile tilapia. Consequently, naturally-infected Nile tilapia with Flavobacterium columnare, showing eroded fins, rigid body figure, and ulcerated body surface, was treated with fucoidan (8 gm/kg ration) for 17 days. Flavobacterium columnare infection was confirmed by isolation on selective medium (cytophaga agar), from the skeletal muscle, tails fins, and gills, giving the typical rhizoid shape. It was also confirmed by Flavobacterium columnare specific PCR using selective primers for Flavobacterium columnare 16S ribosomal DNA. Fucoidan caused decreased the mortalities to nil and cured the eroded fins, the ulcerated body surface, and the rigid body figure. Fucoidan also decreased the tissue damage score to reach the normal histological score.