Vitamins A, E and C play important role in skin homeostasis and protection. Hence, they are extensively used in many cosmetic and cosmeceutic products. However, their molecules are unstable, and do not easily penetrate into the skin, which drastically decreases its efficiency in topical formulations. Liposoluble derivative of the vitamin A - retinyl palmitate, vitamin E - tocopheryl acetate, and vitamin C - tetraisopalmitoyl ascorbic acid, are more stable, and are frequently used as an active ingredient in cosmetic products. Moreover, increased hydrophobicity of these molecules could lead to a higher skin penetration. The aim of this work is to track and compare the absorption of the liposoluble derivatives of the vitamins and their encapsulated form, into the healthy human skin in vivo. We used Confocal Raman Spectroscopy (CRS) that is proven to be helpful in label-free non-destructive investigation of the biochemical composition and molecular conformational analysis of the biological samples. The measurements were performed in the volar forearm of the 10 healthy volunteers. Skin was treated with both products, and Raman spectra were obtained after 15 min, 3 hours, and 6 hours after applying the formulation. 3510 Skin Composition Analyzer (River Diagnostics, The Netherlands) with 785 nm laser excitation was used to acquire information in the fingerprint region. Significant difference in permeation of the products was observed. Whereas only free form of retinyl palmitate penetrate the skin within first 15 minutes, all three vitamin derivatives were present under the skin surface in case of nanoparticulated form.