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Abstract Space use by animals is affected by multiple factors; previous researchers have examined the effects of influences, such as sex, body condition, and population density on home range area. However, evaluating the simultaneous influences of multiple factors on animal space use has been relatively intractable due to sample size limitations. We capitalize on National Ecological Observatory Network (NEON) data to ask what factors determine space use by deer mice (genusPeromyscus). We examined data from 10 years of repeated captures of individually-identified mice at 36 sites across North America. We confirmed previous findings that males have larger home ranges than females and that home range area decreases with increasing animal density. In addition, our large sample size (N = 2,420 individuals) enabled us to examine the interacting influences of these, and other, phenotypic and extrinsic factors using a robust statistical framework. We found that the relationship between body condition and home range area differs between male and female mice, and that habitat type, latitude, and animal density all interact to influence space use. We conclude that data from large ecological networks can be used to examine important behavioral questions that have long eluded investigators.