Opposed-flow flame spread over solid materials has been investigated in the past few decades owing to its importance in fundamental understanding of fires. These studies provided insights on the behavior of opposed-flow flames in different environmental conditions (e.g., flow speed, oxygen concentration). However, the effect of confinement on opposed-flow flames remains under-explored. It is known that confinement plays a critical role in concurrent-flow flame spread in normal and microgravity conditions. Hence, for a complete understanding it becomes important to understand the effects of confinement for opposed-flow flames. In this study, microgravity experiments are conducted aboard the International Space Station (ISS) to investigate opposed-flow flame spread in different confined conditions. Two materials, cotton-fiberglass blended textile fabric (SIBAL) and 1 mm thick polymethyl methacrylate (PMMA) slab are burned between a pair of parallel flow baffles in a small flow duct. By varying the sample-baffle distance, various levels of confinement are achieved (H = 1–2 cm). Three types of baffles, transparent, black, and reflective, are used to create different radiative boundary conditions. The purely forced flow speed is also varied (between 2.6 and 10.5 cm/s) to investigate its interplay with the confinement level. For both sample materials, it is observed that the flame spread rate decreases when the confinement level increases (i.e., when H decreases). In addition, flame spread rate is shown to have a positive correlation with flow speed, up to an optimal value. The results also indicate that the optimal flow speed for flame spread can decrease in highly confined conditions. Surface radiation on the confinement boundary is shown to play a key role. For SIBAL fabric, stronger flames are observed when using black baffles compared to transparent. For PMMA, reflective baffles yield stronger flames compared to black baffles. When comparing the results to the concurrent-flow case, it is also noticed that opposed-flow flames spread slower and blow off at larger flow speeds but are not as sensitive to the flow speed. This work provides unique long-duration microgravity experimental data that can inform the design of future opposed-flow experiments in microgravity and the development of theory and numerical models.