This study compares musculoskeletal pain and leg volume change in Colombian workers in a leather manufacturing company who worked standing and sitting. A cross-sectional study was carried out in a Colombian manufacturing company specializing in producing leather goods for shoes. The sample consisted of 19 workers selected at convenience. Pain intensity and leg volume were recorded at the initial and the final of the working day for workers in sitting and standing posture. Results for seated workers showed that in 8 body parts, musculoskeletal pain increased, and the most significant increase was in the lower back. Results for standing workers showed that in seven body parts, the percentage of musculoskeletal pain increased; additionally, the right thigh-hip body part decreased significantly. Concerning leg volume, it was found that both legs had a significant increase in volume in the seated workers, while in the standing workers, the volume increased but not significantly. The comparison between sitting and standing shows that there was only a significant difference in musculoskeletal pain in right thigh-hip (sitting = 12.36, standing = 6.75; p = 0.026) and left thigh-hip (sitting = 12.77, standing = 6.19; p = 0.009). Seated workers generally reported higher average pain and leg volume levels than standing ones. However, only the thigh-hip pain was statistically significantly higher in the sitting position. We hope our results contribute to the ongoing discussion regarding the relative advantages or disadvantages of prolonged standing versus sitting while working.