Two of the most common infections in poultry, are blackhead, caused by the parasite Histomonas melagridis (HM), and necrotic enteristis (NE) caused by the bacteria Clostridium perfringens (CP). At present there is no treatment of blackhead disease, and the preventive treatment towards NE may soon be banned in the EU. Extracts of aerial parts of Artemisia annua (AA) showed antimicrobial activity in overnight cultures of CP strains isolated from diseased broilers. The hexane extract (HEX) gave the strongest inhibition (MIC=185ppm) while the dichloromethane extract (DCM) gave a weaker inhibition (MIC=270ppm). The dietary incorporation of HEX reduced the population of CP and the severity of the associated small intestinal lesions (P>0.05) in broilers when applying a NE disease model. The antibacterial compounds from HEX and DCM, chrysosplenol and ponticaepoxide, were isolated. This is the first report of activity against CP for these compounds. HEX, DCM and artemisinin were also tested against HM. The two latter showed highest antiprotozoal effect in vitro (MLC=1.0mg/ml and IC50=1.3mg/ml respectively), and were tested in vivo in infected poultry. However, no effect against HM at the given concentrations was observed.