We investigated the serum levels of IL-6 and TNF-α in 30 male alcohol-dependent patients during withdrawal (day 1, 7, and 14) and compared them with the levels obtained from 18 healthy male controls. IL-6 (day 1: T = 2,593, p = 0.013; day 7: T = 2,315, p = 0.037; day 14: T = 1,650, p = 0.112) serum levels were significantly increased at the beginning of alcohol withdrawal. TNF-α (T = 3,202, p = 0.03) serum levels were significantly elevated in the patients' group during the whole period of withdrawal. IL-6 serum levels decreased significantly during withdrawal (F = 16.507, p < 0.001), whereas TNF-α levels did not change significantly (day 1–14). IL-6 serum levels were directly associated with alcohol consumption (r = 0.392, p = 0.047) on day 1. Moreover, the IL-6 serum levels were associated with alcohol craving (PACS total score day 1: r = −0.417, p = 0.022, the score of the obsessive subscale of the OCDS on day 14 [r = −0.549, p = 0.022]), depression (r = −0.507, p = 0.005), and trait anxiety (r = −0.674, p < 0.001) on day 1. We found an association with the duration of active drinking following the last period of abstinence and the TNF-α serum levels (day 1:r = 0.354, p = 0.009; day 7: r = 0.323, p = 0.022; day 14: r = 0.303, p = 0.034) as well as an association with the severity of alcohol dependence measured by the SESA scale (r = 0.454, p = 0.015). Moreover, we found a significant association between the BDNF serum levels and the TNF-α serum levels (r = −0.426, p = 0.021). Our results support an association between alterations in TNF-α and IL-6 serum levels and alcohol consumption.