We present an electrode‐resolved analysis of the performance of platinum‐based abiotically catalyzed glucose fuel cells in realistically simulated tissue fluid (STF) and cerebrospinal fluid (SCF). The presence of amino acids and small organic molecules at physiological concentration leads to a drastic breakdown in fuel cell voltage, resulting in a maximum lifetime of 19 h in STF or 37 h in SCF. The performance loss mainly originates from catalyst poisoning at the anode, which causes 92 % or 80 % of the overall fuel cell voltage loss in STF or SCF, respectively. The results underline the necessity to further investigate and improve catalyst poisoning at the anode under realistic body conditions in order to improve the lifetime of platinum‐based implantable glucose fuel cells.