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Background: Manually derived electrocardiographic (ECG) parameters were not associated with mortality in mechanically ventilated COVID‐19 patients in earlier studies, while increased high‐sensitivity cardiac troponin‐T (hs‐cTnT) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were. To provide evidence for vectorcardiography (VCG) measures as potential cardiac monitoring tool, we investigated VCG trajectories during critical illness. Methods: All mechanically ventilated COVID‐19 patients were included in the Maastricht Intensive Care Covid Cohort between March 2020 and October 2021. Serum hs‐cTnT and NT‐proBNP concentrations were measured daily. Conversion of daily 12‐lead ECGs to VCGs by a MATLAB‐based script provided QRS area, T area, maximal QRS amplitude, and QRS duration. Linear mixed‐effect models investigated trajectories in serum and VCG markers over time between non‐survivors and survivors, adjusted for confounders. Results: In 322 patients, 5461 hs‐cTnT, 5435 NT‐proBNP concentrations and 3280 ECGs and VCGs were analyzed. Non‐survivors had higher hs‐cTnT concentrations at intubation and both hs‐cTnT and NT‐proBNP significantly increased compared with survivors. In non‐survivors, the following VCG parameters decreased more when compared to survivors: QRS area (−0.27 (95% CI) (−0.37 to −0.16, p <.01) μVs per day), T area (−0.39 (−0.62 to −0.16, p <.01) μVs per day), and maximal QRS amplitude (−0.01 (−0.01 to −0.01, p <.01) mV per day). QRS duration did not differ. Conclusion: VCG‐derived QRS area and T area decreased in non‐survivors compared with survivors, suggesting that an increase in myocardial damage and tissue loss play a role in the course of critical illness and may drive mortality. These VCG markers may be used to monitor critically ill patients. [ABSTRACT FROM AUTHOR]