<b><i>Introduction:</i></b> Cigarette smoking is known to modulate brain metabolism and brain function. How the dynamics of these metabolic alterations influence the active performance of higher order cognitive tasks in smokers, compared to non-smokers, is still unclear. The present exploratory study sought to examine the impact of smoking on the “complete” metabolic profile while the participants performed a working memory (N-back) task. <b><i>Methods:</i></b> The study sample consisted of 40 young male healthy participants (smokers [<i>n</i> = 20] and non-smokers [<i>n</i> = 20]). Functional magnetic resonance spectroscopy data were acquired using a 3 T whole-body MR system. Data analysis was performed using Java-based Magnetic Resonance User Interface software, and metabolite ratios with respect to creatine (Cr) were calculated. <b><i>Results:</i></b> On a behavioural level, smokers showed worse performance (measured by d’) than non-smokers. However, we observed significant differences in the metabolite concentrations in smokers compared to non-smokers, which also changed over the course of the N-back task. A significant effect of the group was observed with smokers showing lower glutamate/Cr (Glx/Cr) and choline/Cr (Cho/Cr) ratios than non-smokers. Further, N-acetyl aspartate (NAA/Cr) and Cho/Cr ratios were significantly different during the rest and the task conditions. In addition, our results demonstrated the metabolite interactions (NAA and Cho, Glx and myo-inositol [mI], and Cho and mI). <b><i>Conclusion:</i></b> Further studies are necessary to shed more light on the association between smoking behaviours and metabolic alterations. However, our preliminary findings would assist in this future research to have a complete understanding of the metabolite interactions not only in smoking but also in addiction research.