Purpose <p>Reducing red meat intake in the Western diet is beneficial for health and the environment. However, red meat is nutrient-rich, so understanding the impact of substituting it with other protein sources such as fish or plant-based proteins is essential, especially for vulnerable groups like the elderly and those with chronic diseases. The purpose of this study was to study the postprandial response in serum metabolites in women with Rheumatoid Arthritis (RA) after intake of red meat, fatty fish, and soy protein.</p> Methods <p>Women with RA (<i>n</i> = 24) consumed isocaloric meals that included burgers made from either red meat, fatty fish, or soy protein in a crossover design. Blood samples were taken in fasting state before the meal (0&#xa0;h) and at intervals up to 5&#xa0;h after eating. Nuclear Magnetic Resonance (NMR) analysis quantified serum metabolites, and multivariate models and univariate statistics were applied to compare postprandial metabolite changes across protein sources.</p> Results <p>Postprandial metabolite patterns varied significantly by protein type. The fatty fish meal led to a faster and higher increase in metabolites, including creatinine, isoleucine, valine, and trimethylamine N-oxide, compared to red meat. Unidentified lipids also differed. However, metabolite patterns after soy protein were similar to those after red meat.</p> Conclusion <p>This postprandial crossover trial found that intake of fatty fish lead to a quicker and more pronounced increase in key blood concentrations of metabolites compared to red meat. However, metabolite profiles in serum based on NMR-analysis were similar after intake of soy protein compared to red meat.</p> Trial registration <p>The PIRA (Postprandial Inflammation in Rheumatoid Arthritis) trial is Registered at Clinicaltrials.gov (NCT04247009).</p>