OBJECTIVE To evaluate the efficacy of tulathromycin for prevention of abortion in pregnant ewes when administered within 24 hours after experimental inoculation with Campylobacter jejuni. ANIMALS 20 pregnant ewes between 72 and 92 days of gestation. PROCEDURES All ewes were inoculated with a field strain of C jejuni (8.5 × 108 to 10.6 × 108 CFUs, IV). Eighteen hours later, ewes received either tulathromycin (1.1 mL/45 kg [2.4 mg/kg], SC; n = 10) or sterile saline (0.9% NaCl) solution (1.1 mL/45 kg, SC; sham; 10). Ewes were euthanized immediately after observation of vaginal bleeding, abortion, or completion of a 21-day observation period. Necropsy was performed on all ewes, and tissue specimens were obtained for bacterial culture and histologic examination. RESULTS 1 sham-treated ewe and 1 tulathromycin-treated ewe developed signs of severe endotoxemia and were euthanized within 24 hours after C jejuni inoculation. Seven sham-treated and 2 tulathromycin-treated ewes developed vaginal bleeding or aborted and were euthanized between 4 and 21 days after C jejuni inoculation. The proportion of tulathromycin-treated ewes that developed vaginal bleeding or aborted during the 21 days after C jejuni inoculation (2/9) was significantly less than that for the sham-treated ewes (7/9). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that administration of tulathromycin to pregnant ewes following exposure to C jejuni was effective in decreasing the number of C jejuni–induced abortions. Because of concerns regarding the development of macrolide resistance among Campylobacter strains, prophylactic use of tulathromycin in sheep is not recommended.