Long-distance running and, in particular, running marathons has become an increasingly popular activity among the elderly. The aim of the study was to examine the effects of a marathon effort on the psychomotor performance and catecholamine concentration in runners over 50 years of age. The participants were male runners (n = 28) who completed the 32nd Wrocław Marathon in Poland. The runners’ psychomotor performance was assessed on the basis of their choice reaction times (CRT), heart rate (HR) and running speed measurements. In addition, the adrenaline (A) and noradrenaline (NA) as well as lactate (LA) levels and anaerobic threshold (AT) were measured. The runners’ CRT after crossing the finish line was significantly longer by 50 ms (p < 0.05) in response to each emitted audiovisual stimulus, as compared with baseline. The mean running speed was reduced by 1 km/h between the first speed measurement (5th km of the run) and the last (42.195 km) (p < 0.05). The observed three-fold increase in adrenaline and noradrenaline levels indicates an intense activity of the sympathetic–adrenergic system. The cognitive function levels in the studied marathon runners returned to baseline after 30 min of recovery, and the function of the sympathetic–adrenergic system by seven days after completing the marathon race.