The parallel analysis of multiple factors, such as cytokines, from small sample size is an interesting approach for assessment of in vivo activation signatures and functionality after ex vivo stimulation. One interesting application is for therapy monitoring, such as safety data, pharmacodynamics, evidences for mode-of-action and side effects, particularly useful for accompanying early phase clinical trials. There are different platforms for Multiplex analysis of ligands available. We compared in this study the performance of three different platforms (Luminex Bio-Plex® 200, MesoScale Discovery®, Ella®) which use different ways of achieving parallel measurements of biomarkers from small liquid sample size. We show examples of in house assessment of intra- and inter-assay variations, determination of range and recovery for classical immunological serum markers and discuss advantages and disadvantages for these three platforms in relation to the question addressed.