We study the effects of local environmental conditions affecting the diffuse interstellar band (DIB) carriers within the Upper Scorpius subgroup of the Sco OB2 association. We obtained optical spectra with FEROS, and measured the equivalent widths of five DIBs (at 5780, 5797, 6196, 6379, and 6613 Angstrom) as well as those of absorption lines of di-atomic molecules (CH, CH+, CN) and atoms (KI, CaI) towards 89 targets in the direction of Upper Scorpius. We construct a simple radiative transfer and chemical network model of the diffuse interstellar medium (ISM) sheet in front of Upp Sco to infer the effective radiation field. Both the interstellar radiation field strength, I_UV, and the molecular hydrogen fraction, f_H2, have been derived for 55 sightlines probing the Upp Sco ISM. We discuss the relations between DIB strengths, CH and CH+ line strengths, E(B-V), I_UV, and f_H2. The ratio between the 5780 and 5797 DIBs reveals a (spatial) dependence on the local environment in terms of cloud density and exposure to the interstellar radiation field, reflecting the molecular nature of these DIB carriers.