Ornithosis outbreaks in poultry processing plants are well-described, but evidence for preventive measures is currently lacking. This study describes a case-control study into an outbreak of ornithosis at a poultry processing plant in the East of England, identified following three employees being admitted to hospital. Workers at the affected plant were recruited via their employer, with exposures assessed using a self-completed questionnaire. Cases were ascertained using serological methods or direct antigen detection in sputum. 63/225 (28%) staff participated, with 10% of participants showing evidence of recent infection. Exposure to the killing/defeathering and automated evisceration areas, and contact with viscera or blood were the main risk factors for infection. Personal protective equipment (goggles and FFP3 masks) reduced the effect of exposure to risk areas and to self-contamination with potentially infectious material. Our study provides some evidence of effectiveness for respiratory protective equipment in poultry processing plants where there is a known and current risk of ornithosis. Further studies are required to confirm this tentative finding, but in the meantime respiratory protective equipment is recommended as a precautionary measure in plants where outbreaks of ornithosis occur.