Taking the first corner guide vanes of a large low-speed wind tunnel as the research object. Fully considering the complexity of the structure of guide vane as well as the unevenness of wind load distribution, fluid–structure coupling calculation and analysis are conducted. The local flow field is used as a simplified representation of the full flow field for fluid–structure coupling calculations. The calculation results indicate that when the airflow passes through a guide vane, it is divided into two streams. The overall flow velocity initially increases rapidly and then gradually decreases. The flow velocity on the suction side is greater than that on the pressure side. The pressure on the windward side of the head skin is the highest. The airflow forms a positive pressure zone near the pressure side and a negative pressure zone near the suction side. The single guide vane is subjected to a load directed from the pressure side to the suction side. The deformation of the structure is maximum at the mid-span head skin position. The stress is maximum at the contact between the top bulkhead and the support. After verification, the structure meets the strength requirements under wind load.