The functional group content and the ionic state of functional groups present on a series of surface modified poly(tetrafluoroethylene/hexafluoropropylene) (FEP) copolymers were characterized by electron spectroscopy for chemical analysis (ESCA), contact angle, and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Additionally, after a protein was preadsorbed on these surfaces, in vivo cell (monocyte) adhesion and activation were analyzed. The two proteins in this study were fibrinogen and immunoglobulin-G (IgG). Four modified FEP surfaces were prepared with increasing concentration of carboxyl groups relative to amide groups; ESCA was used to quantify the functional group content. To characterize the ionic state of the functional groups at physiological pH (7.1), the ATR-FTIR spectra were collected at various pH levels. Collectively, the contact angle, ESCA, and ATR-FTIR results suggested that the amide groups were unprotonated and the carboxyl groups were ionized at the physiological pH. The results from the in vitro studies showed that on the fibrinogen preadsorbed surfaces, monocyte adhesion was higher and monocyte activation was lower on the three surfaces that contained carboxyl groups compared to the FEP surface that had only amide groups. Conversely, the results indicated that the surface chemistry had no significant effect on monocyte adhesion or activation on the IgG preadsorbed surfaces.