When pain might occur during an animal experiment, sufficient analgesia is necessary. Metamizole is the third most used postoperative pain medication in animal research. The analgesic effect of metamizole is supposed to last 6-8 h in rodents. Therefore, the supplementation of drinking water with metamizole should be the preferred method to ensure permanent pain relief without unnecessary stressors. The present exploratory study compared the voluntary intake of metamizole-supplemented drinking water (3 mg/ml) between healthy mice of three different mouse strains. After the addition of metamizole to the drinking water, a marginal reduction in body weight was observed in C57BL/6J and BALB/c mice. However, NSG mice displayed a significantly higher body weight loss and reduction of drinking behavior compared with the C57BL/6J and BALB/c strains. The acceptance of metamizole in NSG mice did not increase with a different metamizole formulation. Thus, the mice of the inbred strains C57BL/6J and BALB/c seemed to be able to adapt to the taste of metamizole, while NSG mice were not able to accustom to analgesia within 1 week. Strain-specific habituation should be considered in future animal studies when analgesia is applied via drinking water.