Solid oxide fuel cells (SOFCs) are promising electrochemical power sources with potentially high efficiency. However, long-term performance degradation of SOFC stacks in operation is a critical issue for the commercial application of this technology. Especially the cathode is a sensitive component of the fuel cell, which can be affected by several stability issues. The goal of this work was to investigate the impact of potentially critical operating conditions on the long-term performance of SOFC cathodes, and the influence of the cathode architecture and morphology on the degradation. Long-term degradation experiments were carried out in timeframes between 1500 and 4000 h at temperatures between 700°C and 850°C. The investigated degradation mechanisms were silicon-poisoning and chromium-poisoning in humid atmospheres, as well as the formation of secondary phases at the cathode-electrolyte interface. The potential cathode materials La0.9Ca0.1FeO3-δ (LCF91) and LaNi0.6Fe0.4O3-δ (LNF64) were characterized by the conductivity relaxation method (CR) in van der Pauw geometry. Electrochemical impedance spectroscopy (EIS) measurements were performed on symmetrical cells with model cathodes of the state-of-the-art materials La0.6Sr0.4CoO3-δ (LSC64) and La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) in three different architectures: Conventionally screen-printed cathodes, thin-film cathodes with thicknesses around 0.2 μm and infiltrated nanoscaled LSC64 inside a porous backbone of gadolinia-doped ceria (GDC). In order to identify the causes of degradation, post-test analyses with SEM, STEM and XPS were performed on fresh and degraded samples. For Si-poisoning experiments, quartz glass parts were used as Si source and test gas mixtures of O2 and Ar were humidified to enable formation and transport of volatile Si-species. In all of these experiments humidity affected the cathode performance negatively, but the observed degradation rates were strongly dependent on the cathode morphology. While the dense bulk samples of the CR experiments and the well-defined thin-film model cathodes with relatively low surface/bulk ratio showed a relatively strong performance decrease, the degradation of porous screen-printed and infiltrated cathodes with high surface/bulk ratio was quite low to almost negligible. For Cr-poisoning experiments, wires of an Fe-Cr-Ni alloy were used as Cr-source and ambient air as testing atmosphere. Due to humidity, volatile Cr-species were formed and transported in the reactor. In these experiments, fast degradation was observed for all characterized cathode morphologies, but thin-film cathodes degraded at a higher rate than conventional screen-printed cathodes. Degradation of the cathode-electrolyte-interface was investigated on samples with yttria stabilized zirconia (YSZ) electrolytes and LSC64 cathodes. As expected from similar findings in literature, this material combination caused a strong degradation due to formation of secondary phases at the interface. The cathode architecture had a significant influence as well, since thin-film cathodes degraded much faster than conventional screen-printed cathodes.