3-(4-Chlorophenyl)-3a,4,8,8a-tetrahydro-[1,3,2]dioxaborepino[5,6-d] isoxazoles were synthesized from the reaction of (3-(4-chlorophenyl)-4,5-dihydroisoxazole-4,5-diyl) dimethanol with substituted phenylboronic acids. Crystal structure of 1-(4-(3-(4-chlo rophenyl)-3a,4,8,8a-tetrahydro-[1,3,2]dioxaborepino[5,6-d] isoxazol-6-yl) phenyl) ethanone was studied and the values of selected bond distances (angstrom), bond angles (degrees), and dihedral angles (degrees) were found in agreement with the calculated (DFT, B3LYP/6-311++G(d,p)) values. Antimicrobial activity of these new compounds was also studied against a panel of microorganisms including Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Streptococcus mutans, and Candida albicans. Most of the dioxaborepines exhibited fair activities against these microorganisms. The pMIC values of the compounds were first correlated with Hammett polar substituent constant (sigma) together with lipophilic constant (pi) and statistically significant 2D correlations were obtained. In addition, the pMIC values of the compounds were correlated with some theoretical descriptors and fair 2D-QSAR models with clogP, SAA, and mu as independent variables were obtained.