Despite the social impact of repetitive strain injury (RSI), little is known about its pathophysiological mechanism. The main objective of this study was to assess the local muscle oxygenation (mVO2) and blood flow (mBF) of the forearm in individuals with RSI during isometric contractions of the forearm. We employed the non-invasive optical technique near-infrared spectroscopy to assess forearm VO2 and BF. These variables were assessed at 10%, 20%, and 40% of their individual maximal voluntary strength. Twenty-two patients with RSI symptoms in both arms (bilateral RSI) and 30 healthy age-matched subjects participated in this cross-sectional study. The results showed lower mVO2 during exercise and a reduced mBF after exercise. The results suggest that mVO2 and mVO2 are lower in the forearms of individuals with RSI compared with their controls at similar working intensities. This finding indicates that the underlying vasculature may be impaired. Although these findings contribute to the understanding of RSI, future research is necessary to further unravel the mechanisms of this area.