The electrochemical oxidation process of self-assembled monolayers formed by n-octadecyltrichlorosilane (OTS) molecules on silicon wafers has been studied in a droplet of water by means of in situ water contact angle measurements. The application of different bias voltages between the substrate and a counter electrode placed into the droplet resulted in changes of the chemical nature of the monolayer, which yielded a significant alteration of the surfaces properties. Due to the changes of the wetting properties of the monolayer during the electro-oxidation process a change in the contact angles of the water droplet is concomitantly observed. This allows the in situ monitoring of the electro-oxidation process for large modified areas of several millimeters in diameter. The chosen approach represents an easy way to screen the major parameters that influence the oxidation process. Afterwards, the oxidized regions are characterized by Fourier-transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) measurements, and atomic force microscopy (AFM) investigations to obtain more information about the electro-oxidation process. The observations are correlated to experimental results obtained for oxidations performed on a smaller dimension range in the water meniscus of a conductive, biased AFM tip. A good correlation of the results in the different dimension ranges could be found.