The polymorphic mutation frequencies for 154 Staphylococcus aureus isolates from Chinese bovine clinical mastitis cases were investigated. We found that nearly 29% of the isolates presented as weak mutators, while only two (1.3%) strong mutators were detected. Of the 15 weak mutators that exhibited ciprofloxacin resistance phenotypes, only one isolate was found to be mutS deficient. All of the ciprofloxacin-resistant isolates had the classic ciprofloxacin resistance mutations at codon 80 within the ParC subunit of topoisomerase IV and codon 84/88 within the GyrA subunit of DNA gyrase. The proportion of ciprofloxacin-resistant isolates among the weak mutators (34.1%) was significantly higher than that found in the normomutators (11.4%) and hypomutators (0%) (P < 0.001, Fisher's exact test), suggesting a positive correlation between weak mutators and ciprofloxacin resistance.