Objectives To compare high-resolution (HR) and conventional (C) settings of high-spatial-resolution computed tomography (CT) for software volumetry of ground-glass nodules (GGNs) in phantoms and patients. Methods We placed −800 and −630 HU spherical GGN-mimic nodules in 28 different positions in phantoms and scanned them individually. Additionally, 60 GGNs in 45 patients were assessed retrospectively. Images were reconstructed using the HR-setting (matrix size, 1024; slice thickness, 0.25 mm) and C-setting (matrix size, 512; slice thickness, 0.5 mm). We measured the GGN volume and mass using software. In the phantom study, the absolute percentage error (APE) was calculated as the absolute difference between Vernier caliper measurement-based and software-based volumes. In patients, we measured the density (mean, maximum, and minimum) and classified GGNs into low- and high-attenuation GGNs. Results In images of the −800 HU, but not −630 HU, phantom nodules, the volumes and masses differed significantly between the two settings (both p < 0.01). The APE was significantly lower in the HR-setting than in the C-setting (p < 0.01). In patients, volumes did not differ significantly between settings (p = 0.59). Although the mean attenuation was not significantly different, the maximum and minimum values were significantly increased and decreased, respectively, in the HR-setting (both p < 0.01). The volumes of both low-attenuation and high-attenuation GGNs were not significantly different between settings (p = 0.78 and 0.39, respectively). Conclusion The HR-setting might yield a more accurate volume for phantom GGN of −800 HU and influence the detection of maximum and minimum CT attenuation.