Our proteomics approach revealed significant associations between changes in the plasma proteome within the first days of sepsis and mortality as well as disease severity.

We identified and characterised the underlying protein networks, providing insights beyond traditional clinical assays.

Key processes within the innate immune system, such as complement activation, were associated with sepsis outcome but are not typically assessed in routine diagnostics.

Future investigations should focus on the role of individual proteins and their potential as diagnostic or therapeutic targets.

This prospective, multicentre observational cohort study included 363 patients with sepsis recruited from five university hospitals in Germany between March 2018 and April 2023.

Out of 363 patients, 224 (62%) survived, and 139 (38%) did not survive the 30-day period.

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