Introduction: Near-infrared spectroscopy (NIRS) can be used to monitor the oxygen saturation of hemoglobin in any given superficial tissue. However, the measurements provided by different oximeters can vary a lot. Little is known about the specific patient characteristics that could affect the inter-device agreement of tissular oximeters. This study aimed to evaluate the association between the quantity of subcutaneous fat (assessed by skinfold thickness) and the inter-device agreement of two tissue oximeters, the INVOS 5100c and the Equanox 7600. Methods: In this prospective cohort study, tissue saturations and skinfold thickness were measured at four different sites on both sides of the body in healthy adult (≥18 years old) volunteers. The association between the quantity of subcutaneous fat (assessed by skinfold thickness) and the inter-device agreement (absolute difference between the oximetry values provided by the two oximeters) was first assessed with a Pearson's correlation and a scatter plot. Subsequently, a linear mixed model was used to evaluate the impact of the subcutaneous fat and other covariables (age, sex) on the inter-device agreement while adjusting for the repeated measurements across different sites for the same volunteers. Results: From January to March 2015, 53 healthy volunteers were included in this study with ages ranging between 20 and 81 years old, on which a total of 848 measures were taken. Higher skinfold measures were associated with an increase in the difference between measures provided by both oximeters (Slope = -0.59, Pearson correlation coefficient = -0.51, p < 0.001). This observed association persisted in a linear mixed model (-0.48 [95% confidence interval {CI}-0.61 to -0.36], p < 0.001). The sex of the volunteers also influenced the inter-oximeter agreement (Women:-5.77 [95%CI -8.43 to -3.11], p < 0.001), as well as the forearm sites (Left forearm: −7.16 [95%CI -9.85 to –4.47], p < 0.001; right forearm: −7.01 [95%CI -9.61 to −4.40], p < 0.001). Conclusion: The quantity of subcutaneous fat, as well as the sex of the volunteers and the measurement sites, impacted the inter-device agreement of two commonly used oximeters. Given these findings, monitoring using tissue oximetry should be interpreted with great care when there is a significant quantity of subcutaneous fat.