This double-blind, randomised, placebo-controlled, parallel group study examined the effects of a multivitamin–mineral supplement with guaraná (Berocca Boost Performance®) on aspects of cognitive performance and self-reported mental fatigue during sustained, effortful mental processing. The acute effects of a single dose of either the vitamin/mineral/guaraná or placebo in an effervescent drink were assessed in 129 healthy adults (18–24 years). The Cognitive Demand Battery (CDB) was used for testing. This is a 10-min battery comprising of Serial Threes subtraction (2 min), Serial Sevens subtraction (2 min), Rapid Visual Information Processing [RVIP] (5 min) and a ‘Mental Fatigue’ visual analogue scale. Participants firstly completed the CDB twice (practice and baseline) and then consumed their treatment. Thirty minutes following consumption of the treatment the participant completed the CDB six times consecutively. The most notable findings were that the active treatment was associated with increased speed and accuracy in the performance of the RVIP throughout the 60 min of testing. The active treatment was also associated with reduced ratings of subjective mental fatigue significantly so during the later, more fatiguing repetitions. This research supports the previous findings of the psychoactive properties of guaraná. It also provides for the first time evidence in humans that a multivitamin–mineral preparation containing guaraná can improve cognitive performance and reduce mental fatigue associated with sustained mental effort.