There is a great need for biomarkers in epilepsy, particularly markers of epileptogenesis. A first seizure will lead to epilepsy in 20-45 % of cases, but biomarkers that can identify these individuals are missing. The purpose of this study was to identify potential biomarkers of epilepsy/epileptogenesis in a cohort of adults with new-onset seizures, using quantitative proteomic analysis. Plasma was collected from 55 adults with new-onset seizures and sufficient follow-up to identify epilepsy. After a follow up period of two years, 63.6 % of the cohort had a diagnosis of epilepsy, whereas 36.4 % of patients only had a single seizure. Plasma proteins were extracted and labelled with tandem mass tags, then analyzed using mass spectrometry approach. Proteins that were up- or downregulated by ≥20 % and with a p-value of <0.05 were considered as differentially expressed and were also annotated to their processes and pathways. Several proteins were differentially expressed in the epilepsy group compared to controls. A total of 1075 proteins were detected, out of which 41 proteins were found to be significantly dysregulated in epilepsy patients. Many of these have been identified in experimental studies of epilepogenesis. We report plasma proteome profiling in new-onset epilepsy in a pilot study with 55 individuals. The identified proteins could be involved in pathways associated with epileptogenesis. The results should be seen as hypothesis-generating and targeted, confirmatory studies are needed.