Mink urinary tract disease (MUTD) often presents as urolithiasis and/or cystitis and is known as an important cause of mortality in mink kits during the early growth season. Antimicrobial flock treatment has been routinely applied as preventive/therapeutic protocol on Danish mink farms with increased mortality associated with MUTD. The therapeutic effect of this treatment strategy has not previously been investigated. In this study, we applied controlled parallel group treatment trials to assess the effect of sulfadiazine/trimethoprim and amoxicillin treatment on mortality associated with MUTD in mink kits. On farm A, eight mink kits were diagnosed with MUTD post mortem in the treatment group (n = 1920, sulfadiazine/trimethoprim treatment: 30 mg/kg, q 24 h, P.O for 5 days) compared to 16 in the untreated control group (n = 1920). No significant difference in mortality associated with MUTD were found between the treatment and the control group using the Fisher’s exact test (P = 0.15). Treatment group 2 (n = 1920, amoxicillin treatment: 14 mg/kg q 24 h, P.O for 5 days) and treatment group 3 (n = 2088, amoxicillin treatment: 7.5 mg/kg q 24 h, P.O for 5 days) were investigated on farm B. Eight and four mink kits were diagnosed with MUTD post mortem in group 2 and 3, respectively. No difference between occurrence of MUTD were found between the control group and treatment group 2 (P = 0.42) or treatment group 3 (P = 0.75). No significant difference between final body weights or weight gain were found between treatment and control weighing groups on farm A or B. In conclusion, antimicrobial treatment administered in the feed showed no significant effect on weight gain or mortality associated with MUTD on the farms included in this study.