Establishment and spread of Ornithonyssus sylviarum were documented through time on sentinel hens (50 per house of 28,000–30,000 hens) in the first egg production cycle of three large commercial flocks (12 houses) of white leghorn hens. Mites were controlled using acaricide, and the impacts of treatment on mite populations and economic performance were documented. Mite prevalence and intensity increased rapidly and in tandem for 4–8 weeks after infestation. Intensity declined due to immune system involvement, but prevalence remained high, and this would affect mite sampling plan use and development. Early treatment was more effective at controlling mites; 85% of light infestations were eliminated by a pesticide spray (Ravap), versus 24% of heavy infestations. Hens infested later developed lower peak mite intensities, and those mite populations declined more quickly than on hens infested earlier in life. Raw spatial association by distance indices (SADIE), incorporating both the intensity and distribution of mites within a house, were high from week-to-week within a hen house. Once adjusted spatially to reflect variable hen cohorts becoming infested asynchronously, this analysis showed the association index tended to rebound at intervals of 5–6 weeks after the hen immune system first suppressed them. Large, consistent mite differences in one flock (high vs. low infestation levels) showed the economic damage of mite parasitism (assessed by flock indexing) was very high in the initial stages of mite expansion. Unmitigated infestations overall reduced egg production (2.1–4.0%), individual egg weights (0.5–2.2%), and feed conversion efficiency (5.7%), causing a profit reduction of $0.07–0.10 per hen for a 10-week period. Asynchronous infestation patterns among pesticide-treated hens may have contributed to a lack of apparent flock-level economic effects later in the production cycle. Individual egg weights differed with mite loads periodically, but could be either higher or lower, depending on circumstances and interactions with hen weight. Individual hen weight gains were depressed by high/moderate mite loads, but the heavier hens in a flock harbored more mites. This led to compensatory weight gains after mites declined. Tradeoffs between resource allocation to body growth or production versus immune system function appeared to be operating during the early and most damaging mite infestation period, when high egg production was beginning and the hens were gaining weight. The results were related to other studies of mite impact on domestic hens and to wild bird–ectoparasite studies. Much of the mite economic damage probably is due to engaging and maintaining the immune response.