The impact of long-term exposure of La0.6Sr0.4CoO3 − δ to SO2-containing atmospheres was investigated. In-situ dc-conductivity relaxation measurements showed a decrease in the chemical surface exchange coefficient of oxygen (kchem) during the course of 1000 h in an atmosphere with either a few ppb or 2 ppm SO2 at 700 °C. Post-test analyses by scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and analytical transmission electron microscopy indicated that SrSO4 crystals with diameters of 100 nm–1 μm are formed during the degradation, in addition to a nanocrystalline 100–300 nm thick multi-phase layer and LaCoO3 − δ at grain boundaries. In order to regenerate the degraded sample, a thermal treatment was applied. It could be shown that a partial re-activation of the degraded specimen takes place at 750–850 °C even in an atmosphere with 2 ppm SO2. This regeneration is ascribed to the in-situ formation of catalytically active LaCoO3 − δ nanoparticles at the surface. However, a subsequent degradation follows independently of the SO2 content of the atmosphere when the sample is kept for 1000 h at 850–900 °C. Post-test analyses indicate that this effect is due to a strong grain growth of the LaCoO3 − δ nanocrystals which leads to a loss in the catalytic activity.