Cellulitis has emerged as an economically important disease of broiler chickens. The impact of environmental risk factors on the incidence of cellulitis has not been evaluated in the United States. Escherichia coli (E. coli), the causative agent, is introduced through skin scratches during the grow out. Our previous work suggested that the litter was an important reservoir for cellulitis-associated E. coli. We hypothesized that factors contributing to a positive environment for E. coli growth would increase the opportunity for exposure of a broiler to an infectious dose of E. coli, capable of initiating a cellulitis lesion. This prospective study of 304 flocks on five farms from two integrated broiler companies was conducted to determine the effect of environmental factors on the prevalence of cellulitis in California broiler flocks. Environmental variables included temperature, wind velocity, and relative humidity (RH) at the litter surface. Litter variables measured included E. coli and total gram-negative bacteria load (colony forming units/g dry matter), water activity, and pH. Management variables such as clean out, the number of flocks reared on the same litter (litter run, LR), and downtime (DT) between flocks were also evaluated. Cellulitis ranged from 0.197% to 6.04%. Significant associations were identified using linear regression between farm, LR, DT, ambient temperature during the brooding period, gram-negative bacteria load in the litter during the brooding period, RH mid–grow out, and E. coli load late in the grow out. The significant variation in the rate of cellulitis between farms combined with the strong association of LR and DT with cellulitis demonstrated that management choices were highly influential in this disease syndrome. Based on these data and our previous findings, managers would be advised to increase DT between flocks and perform a total clean out of the house when a flock processes with a high incidence of cellulitis.