Alcohol dependence is a common public health problem and epigenetics may offer new aspects in understanding the biological and genetic underpinnings and improve treatment of this complex disease. Supposedly, methylation and hydroxymethylation are altered in brain tissues and in synapse-related genes due to chronic alcohol intake and during withdrawal. To assess potential epigenetic changes after cessation of chronic alcohol intake, we compared 23 alcohol-dependent individuals during inpatient alcohol detoxification with 13 carefully matched controls. Blood samples were taken on the day of admission, after one and after two weeks at the end of inpatient treatment. Genome-wide global methylation and global DNA hydroxymethylation were compared across groups. There were significant differences in global methylation across time from admission to one and two weeks of inpatient withdrawal (p < 0.001). These findings were paralleled to changes in global DNA hydroxymethylation across time when age was employed as a cofactor (p < 0.001). Several potentially influencing variables like severity of withdrawal, dose of withdrawal medication and alcohol intake before admission did not yield significant influence on epigenetic changes. The results confirm previous findings of significant alterations of epigenetic patterns during alcohol intoxication and present for the first time hydroxymethylation changes in these individuals.