Objectives To investigate the improvement of symptoms and sleep in children with monosymptomatic nocturnal enuresis (MNE) treated with desmopressin (DDAVP). Methods A total of 69 children with MNE who were treated in our clinic from 2018 to 2020 were selected for a 12-week follow-up study of DDAVP treatment. After 12 weeks, the children were divided into improvement group and non-improvement group according to the remission of enuresis, and the effect of DDAVP treatment on enuresis symptoms and sleep quality was analyzed. Results Among the 69 children with MNE enrolled at baseline, 7 dropped out of the follow-up, and 62 were eventually included, including 34 boys and 28 girls, with an average age of (8.77±1.94) years. In all MNE children treated with DDAVP, there were statistically significant differences in the number of enuresis nights, total score of the children's sleep habits questionnaire (CSHQ), occurrence time of enuresis, and sleep time on weekdays and weekends between baseline, weeks 4, 8 and 12 (P<0.05). Compared with baseline, the number of enuresis nights and the total score of CSHQ at week 12 were significantly decreased, and the occurrence time of enuresis and sleep time on weekdays and weekends were significantly prolonged, and the differences were statistically significant (P<0.05). Compared with the non-improvement group (n=22), the improvement group (n=40) at week 8 and 12 had lower CSHQ scores, significantly longer enuresis occurrence time, sleep time on weekdays and weekends, and fewer enuresis nights per week, and the differences were statistically significant (P<0.05). In terms of CSHQ scores at 8 levels, there were statistically significant differences in the scores of sleeping habits, sleep latency, bedtime duration, sleep anxiety, night waking, parasomnias and daytime sleepiness in the improvement group (P<0.05), while there was statistically significant difference only in bedtime duration in the non-improvement group (P<0.05).Conclusion DDAVP treatment for 12 weeks can significantly improve the symptoms and sleep quality of children with MNE.