Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome. Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33 °C or TTM at 36 °C for 24 h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72 h after OHCA. The primary endpoint was neurological outcome. Results: Median (quartile 1 - quartile 3) tau-A (ng/ml) values were 58 (43-71) versus 51 (43-67), 72 (57-84) versus 71 (59-82) and 76 (61-92) versus 75 (64-89) for good versus unfavourable outcome at 24, 48 and 72 h, respectively (pgroup = 0.95). Median tau C (ng/ml) values were 38 (29-50) versus 36 (29-49), 49 (38-58) versus 48 (33-59) and 48 (39-59) versus 48 (36-62) (pgroup = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48 h; tau-A: 0.51 and tau-C: 0.51). Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.