Background: Impaired systemic tissue oxygenation and microvascular perfusion are associated with adverse outcomes in patients with acute respiratory distress syndrome (ARDS). Tissue oxygenation and microvascular reactivity, assessed by using near-infrared spectroscopy (NIRS), are correlated with disease severity in critically ill populations. This study aimed to detect alterations in these factors and their ability to predict outcomes in patients with ARDS. Methods: We performed NIRS measurements on the first (Day 1) and third (Day 3) days after ARDS diagnosis in 29 patients. We recorded the baseline forearm muscle oxygen saturation (StO₂) and calculated the deoxygenation slope (Deoxy) and reoxygenation (Reoxy) slope. We divided the subjects into 28-day survival and non-survival subgroups to compare microcirculatory and oxygenation status differences. Results: The Day 1 StO₂ values were significantly higher for the survival subgroup (60.1 ± 13.5%) than the non-survival subgroup (47.2 ± 6.9%) (p = 0.025). The ROC curve showed that Day 1 StO₂ was a significant predictor of 28-day mortality (p = 0.025). There was no significant difference between the Deoxy and Reoxy slopes of the two groups (p > 0.05). The ROC of the Day 1 Reoxy slope for survival prediction (AUC0.74) was not statistically significant (p = 0.074). Conclusions: Our study showed poor survival outcomes in patients who had lower skeletal muscle StO₂ values in early-stage ARDS. NIRS measurements may provide prognostic value for the survival outcomes in patients with this syndrome.