Resorption cavities formed during bone remodeling may act as “stress risers” and impair cancellous bone strength, but biomechanical analyses of the effects of stress risers have been limited. To provide further insight, we assessed the theoretical biomechanical effects of virtually-added resorption cavities in cancellous bone specimens spanning a wide range of bone volume fraction (BV/TV = 0.05–0.36) and across different anatomic sites (hip and spine) and species (human and canine). Micro-CT scans of 40 cubes of cancellous bone were converted into nonlinear finite element models (voxel element size ∼ 20 µm) for strength assessment. In each model, uniform trench-like resorption cavities with nominal dimensions 500 µm (length) × 200 µm (width) × 40 µm (depth), were virtually added either at random locations throughout the specimen, or, preferentially at locations of high tissue-level strain. We found that cancellous bone strength (p < 0.0001) and its relation with BV/TV (p < 0.001) were both altered by the virtual addition of the resorption cavities. When the resorption cavities were added at random locations throughout the specimen, the reduction in strength did not depend on BV/TV or anatomic site or species. When the resorption cavities were instead added preferentially at locations of high tissue-level strain, the effect was accentuated and was greatest in low-BV/TV bone. We conclude that, in theory, uniform-sized resorption cavities can reduce cancellous bone strength over the full range of BV/TV and across species, and the effect is larger if the cavities occur at highly strained locations in low-BV/TV bone. © 2012 American Society for Bone and Mineral Research.