Previous studies have shown abnormal thyroid hormone profiles during cardiac arrest. We explored this association further by characterizing plasma thyroid hormone profiles in 473 patients with out-of-hospital cardiac arrest and correlating them with clinical outcomes. Paramedics collected blood at the end of attempted resuscitation regardless of success. Bloods were collected and processed in a similar manner from 18 control subjects randomly selected from the community. Total thyroxine and total triiodothyronine were lower and reverse triiodothyronine and thyrotropin were higher in cardiac arrest patients than control subjects (all p < 0.001). Except for reverse triiodothyronine, findings were similar for a subgroup of cardiac arrest patients considered to be previously healthy (n = 30). Being discharged alive was associated with total thyroxine, total triiodothyronine and reverse triiodothyronine concentrations closer to the control range and thyrotropin concentrations farther from it, namely higher. In a multivariate stepwise model, only total triiodothyronine and thyrotropin were significantly associated with outcome. Whether these profoundly abnormal profiles represent a pre-existing state or a sudden change of thyroid hormone concentrations cannot be answered with this retrospective study. These observations suggest that thyroid hormones may play a role in the etiology of cardiac arrest, its prognosis, or both.