In this study, we aimed to evaluate the prognostic significance of collagens in patients with oral squamous cell carcinoma (OSCC). Plasma proteomics data from 40 OSCC patients and 33 healthy controls, generated using the Olink Explore 3072 platform, along with microarray gene expression data from 29 OSCC tumours, 21 clinically normal tissues contralateral to tumour (NTCT), and 14 healthy controls, were analysed to assess expression levels of collagens and their associations with clinicopathological variables and survival outcomes. Eleven collagen peptides were detected in plasma. Higher circulating levels of collagen type III alpha 1 chain (COL3A1) propeptides were associated with improved overall survival and longer disease-free time (p < 0.05). Penalised Cox regression using the least absolute shrinkage and selection operator (LASSO) supported COL3A1 propeptide as a survival-associated feature. Comparison of protein profiles between COL3A1-low and COL3A1-high patients identified neutrophil degranulation as the most significantly enriched pathway. Microarray differential expression analysis showed COL3A1 mRNA to be significantly upregulated in tumour tissues compared with NTCT and healthy controls (FDR < 0.05). Circulating COL3A1 propeptide shows potential as a prognostic biomarker for OSCC and may reflect systemic immune-related alterations.