Single walled carbon nanotubes (SWNTs) possess unique structural and functional properties. Their ability to be functionalized with different biomolecules makes them excellent candidates for biomedical applications like targeted drug delivery and cancer diagnostics. However, prior to use in therapeutic applications, biocompatibility of SWNTs needs to be thoroughly investigated. Blood is a living tissue and contains cells which can potentially interact with SWNTs during the drug delivery process. The interaction of leukocytes in blood with the SWNTs can provide information regarding the immune response of the host to the nanotubes. Here, we evaluated the acute immune response of leukocytes in blood to SWNTs via (a) direct interaction, due to the presence of SWNTs in circulation and (b) indirect interaction, due to the presentation of SWNTs to leukocytes via antigen presenting cells. These SWNTs were non-covalently functionalized with single stranded DNA (ss-DNA) that acts as a surfactant for suspending SWNTs in aqueous solutions and also serves as a backbone for attaching and transporting different biomolecules. Isolation of cells from blood was done using density gradient centrifugation. Early activation markers were used to study the activation of different leukocyte subpopulations and any activation results in changes of these markers. Flow cytometry was done to analyze the different subpopulations. Results of our study demonstrated that ss-DNA functionalized SWNTs do not elicit an immune response from leukocytes in blood via direct or indirect interaction. This intensive study demonstrates the biocompatibility of single walled carbon nanotubes and paves the way for their safe use in drug delivery and cancer therapeutics without cytotoxicity.