AbstractThis study reports the synthesis of a new series of pyrazole‐isoxazolines, at very good yields, from the cyclocondensation reaction of pyrazole‐enaminones with hydroxylamine hydrochloride. Dehydration of the pyrazole‐isoxazolines furnished another new series of the respective pyrazole‐isoxazoles, at excellent yields. Both series of the obtained compounds were screened for antimycobacterial activity, and compounds 4 f and 5 c showed significant inhibition of bacterial growth with a time‐ and concentration‐dependent bactericidal effect. Cytotoxicity tests in VERO cell line did not indicate toxicity of compounds 4 f and 5 c regarding cellular prediction, NO production or dsDNA release. However, both compounds were associated with an increase in total ROS levels, providing induction of oxidative stress, but without compromising cellular targets. These results highlight compounds 4 f and 5 c as promising candidates for antimycobacterial treatment with a favorable safety profile.