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Q fever is a zoonotic disease caused by Coxiella burnetii. The pathogen is prevalent in ruminants (goats, sheep, cows), which are the main sources of human infection. In the cattle industry around the world, animal (15 to 20%) and herd (38 to 72%) level prevalences of C. burnetii are high. Vaccination of ruminants against Q fever is considered important to prevent spreading of the disease and risk of infection in humans. However, published information on side effects of the Q fever vaccination under field conditions is limited for cows. The objective of this study was to investigate the effect of the phase I C. burnetii inactivated vaccine Coxevac on body temperature and milk yield in dairy cows. In 2 experiments, a total of 508 cows were randomly divided into 2 groups to determine the effect of first vaccination on body temperature and milk yield. The C. burnetii serostatus of all cows was tested before vaccination with an indirect ELISA. The first experiment took place in the teaching and research barn of the Clinic of Animal Reproduction at the Freie Universität Berlin. Temperature was measured vaginally in 10 cows in a crossover design. The second experiment was conducted on a commercial dairy farm. Milk yield of 498 cows was measured 1 wk before and 1 wk after vaccination. In a subset of 41 cows, temperature was measured rectally. In both experiments, body temperature increased significantly after vaccination (1.0 ± 0.9°C and 0.7 ± 0.8°C). A significant difference was also found in body temperature between vaccinated and control cows. Thirty percent of the vaccinated animals in experiment 1 showed reversible swelling at the injection site as a reaction to the vaccination. The results indicate that vaccination against Q fever causes a transient increase of body temperature that peaks in the first 12 to 24 h and declines after that. In experiment 2, vaccinated cows (26.8 ± 0.39 kg/d) produced significantly less milk than did control cows (28.2 ± 0.44 kg/d) 7 d after first vaccination. The cumulative milk loss after first vaccination was influenced by an interaction between C. burnetii serostatus and average milk yield 7 d before first vaccination. This was considered as part of the physiological immune response. Three out of 10 vaccinated animals in experiment 1 showed painful swelling of the skin at the injection site, which had a maximum size of 14.0 × 14.0 × 1.1 cm. In conclusion, a transient increase of body temperature and a decrease in milk yield is prevalent after Coxevac vaccination.