Background: The self-medication hypothesis attempts to explain the extraordinary high levels of cigarette smoking in schizophrenia. It rests on three main explanations; patients may smoke as an attempt to reduce their cognitive deficits, their symptoms or the antipsychotic side-effects. In a previous report, our team detected a beneficial attentional and working memory performance in smoking first episode psychosis patients compared to non-smokers soon after their stabilization. Methods: In the present analyses we examine differences in the course of those deficits 12-months after the instauration of the antipsychotic treatment, exploring also smoking associations to symptoms and medication side-effects. Neuropsychological assessments were performed at baseline, month 6 and 12, using a computerized battery that included measures of sustained attention (Continuous Performance Test CPT- O), selective attention (Stroop Interference task) and working memory (CPT- XO). Patients included met the criteria of fitting in the same smoking category throughout the study: non-smoker (n=15; 0 cigarettes/day), smoker (n=26; >15 cigarettes/day). Results: Smoking patients lost their superior baseline performance, which probably was obtained through nicotinic stimulation, at the 6-12months assessments due to a static course of deficits. The non-smoking patients showed significant improvements, probably derived from the antipsychotic treatment. Discussion: Nicotine in tobacco smoking might improve attention and working memory in a similarly modest degree than atypical antipsychotics. Smoking might reflect an effort to ameliorate these cognitive dysfunctions. Smoking was not associated with fewer extrapyramidal side-effects or symptoms. Moreover, nicotine consumers worsen their symptoms over the first year, result that supports smoking as a marker of a more severe illness.