Regular consumption of tomato and its products is being consistently associated with lower risk of several types of cancer and, to a lesser extent, coronary heart disease. Among the many tomato components credited with healthful properties, carotenoids and particularly lycopene are being actively investigated. Given the recognized role of immune/inflammatory processes in atherogenesis, the effects of a tomato-based drink (Lyc-o-Mato), which was previously shown to afford DNA protection from oxidative stress, on the modulation of immune and inflammatory markers (by enzyme immunoessay), on basal lymphocyte DNA damage (by comet assay), and on F2-isoprostane excretion (by LC-MS/MS), were investigated in 26 healthy young volunteers. In a placebo-controlled, double-blind, crossover study, Lyc-o-Mato (5.7 mg of lycopene, 3.7 mg of phytoene, 2.7 mg of phytofluene, 1 mg of beta-carotene, and 1.8 mg of alpha-tocopherol) or a placebo drink (same taste and flavor, but devoid of active compounds) were given for 26 days, separated by a wash-out period. During the study subjects maintained their habitual, hence unrestricted, diet. TNF-alpha production by whole blood was 34.4% lower after 26 days of drink consumption, whereas the other parameters were not significantly modified by the treatment. In turn, modest effects of the regular intake of a tomato drink, providing small amounts of carotenoids, were found on the production of inflammatory mediators, such as TNF-alpha, in young healthy volunteers. Future intervention trials in subjects with low carotenoid status and/or compromised immune system will resolve the issue of whether carotenoids modulate immune parameters in humans.