The synthesis and antimicrobial activity of a new series of 5-ethylsulphonyl-2-(substituted-phenyl/substituted-benzyl and/or phenylethyl)benzoxazole derivatives (3a-3t) except 3a, 3g, 3h, 3k [R.S. Pottorf, N.K. Chadha, M. Katkevies, V. Ozola, E. Suna, H. Ghane, T. Regberg, M.R. Player, Tetrahedron Lett. 44 (1) (2003) 175] were described. The in vitro antimicrobial activity of the compounds was determined against some Gram-positive, Gram-negative bacteria, a fungi Candida albicans and their drug-resistant isolates in comparison with standard drugs. Antimicrobial results indicated that the synthesized compounds possessed a broad spectrum of activity with MIC values 250-7.81 microg/ml. While all compounds are less potent than fluconazole against C. albicans, most of them are more potent than fluconazole against C. albicans isolate.