A combined computational fluid dynamics and structural stress investigation was conducted to study the response of steel structures to fire. The structure was a two-story building with six rooms. The fire was confined to one room on the first floor. The free convection of air and thermal radiation were both included in the analysis. The governing differential equations of flow and energy were solved by FLUENT. The air turbulence was modeled by the standard k-epsilon model, and the radiation was simulated by the Discrete Transfer Radiation Model. The temperature of the beams and columns were subsequently used in the thermal stress analysis to obtain the deflection and total strain using ANSYS. The result of FLUENT analysis indicates that the air velocity was high in the middle of the room above the fire and adjacent to the ceiling. The temperatures of the beams and columns generally decreased away from the center, with a more rapid decrease toward the ends. It was also observed that radiation played an important role in fire modeling (i.e., 20-40% of the heat transfer took place by radiation). The ANSYS analysis indicated a maximum deflection of 28.66 mm at a beam-column joint in the room with fire at the first level of the structure. The corresponding steel column design load capacity is exhausted after 34 minutes of standard ISO 834 fire due to a combined temperature and gravity loads. The maximum strain was observed at the center of the longitudinal beam, and the minimum was on the steel members of the second floor.