The aim of this study was to evaluate the effects of a simulated porcelain-fused-to-metal (PFM) firing process on the surface, corrosion behavior, and cell culture response of two cobalt-chromium (Co-Cr) dental alloys. Two Co-Cr dental alloys were tested-a high and a low molybdenum (Mo)-containing alloys. Before PFM firing, as-cast alloy specimens were examined for their microstructure, surface composition, and hardness. Corrosion behavior was evaluated using electrochemical impedance spectroscopy tests. Mouse 3T3 fibroblasts were exposed indirectly to specimens and MTT cell proliferation assays were performed after 3 and 6 days. The cell culture medium exposed to specimens was analyzed for metal ion release. After firing, similar alloy specimens were examined for the same properties. The tests showed that the PFM firing changed both alloys' microstructures and hardness values. After PFM firing, the corrosion resistance of the low Mo-containing Co-Cr alloy decreased statistically, which corresponded with a reduction of Cr and oxygen levels in the surface oxides via X-ray photoelectron spectroscopy. Also, the MTT assay of this alloy decreased significantly corresponding with an obvious increase of Co release after the firing. For the high Mo-containing Co-Cr alloy, the surface composition, corrosion resistance, and cell culture response were not significantly changed after PFM firing. The results suggested that the corrosion resistance and biocompatibility of the low Mo-containing Co-Cr alloy decreased after PFM firing, whereas the firing process had little effect on the same properties of the high Mo-containing Co-Cr alloy.