Sulfonamides are the second most used antibiotic class in veterinary medicine and applied to livestock to treat bacterial infections. Subsequently, they are spread onto agricultural soils together with the contaminated manure used as fertilizer. Both manure and antibiotics affect the soil microbial community. However, the influence of different liquid manure loads on effects of antibiotics to soil microorganisms is not well understood. Therefore, we performed a microcosm experiment for up to 32 d to clarify whether the function and structure of the soil microbial community is differently affected by interactions of manure and the antibiotic sulfadiazine (SDZ). To this end selected concentrations of pig liquid manure (0, 20, 40, 80 g kg–1) and SDZ (0, 10, 100 mg kg–1) were combined. We hypothesized that incremental manure amendment might reduce the effect of SDZ in soils, due to an increasing sorption capacity of SDZ to organic compounds. Clear dose-dependent effects of SDZ on microbial biomass and PLFA pattern were determined, and SDZ effects interacted with the liquid manure application rate. Soil microbial biomass increased with incremental liquid manure addition, whereas this effect was absent in the presence of additional SDZ. However, activities of enzymes such as urease and protease were only slightly affected and basal respiration was not affected by SDZ application, while differences mostly depended on the concentration of liquid manure. These results illustrated that the microbial biomass and structural composition react more sensitive to SDZ contamination than functional processes. Furthermore, effects disproportionally increased with incremental liquid manure addition, although extractable amounts of SDZ declined with increasing liquid manure application.