Globally, Avipoxvirus species affect over 230 species of wild birds and can significantly impair survival. During banding of nine grassland songbird species (n = 346 individuals) in southwestern Wisconsin, USA, we noted species with a 2–6% prevalence of pox-like lesions (possible evidence of current infection) and 4–10% missing digits (potential evidence of past infection). These prevalences approach those recorded among island endemic birds (4–9% and 9–20% for the Galapagos and Hawaii, respectively) for which Avipoxvirus species have been implicated as contributing to dramatic population declines. Henslow's Sparrow Ammodramus henslowii (n = 165 individuals) had the highest prevalence of lesions (6.1%) and missing digits (9.7%). Among a subset of 26 Henslow's Sparrows from which blood samples were obtained, none had detectable antibody reactive to fowlpox virus antigen. However, four samples (18%) had antibody to canarypox virus antigen with test sample and negative control ratios (P/N values) ranging from 2.4 to 6.5 (median 4.3). Of four antibody-positive birds, two had lesions recorded (one was also missing a digit), one had digits missing, and one had no signs. Additionally, the birds with lesions or missing digits had higher P/N values than did the antibody-positive bird without missing digits or recorded lesions. This study represents an impetus for considering the impacts and dynamics of disease caused by Avipoxvirus among North American grassland bird species.