Objective: To investigate the effect of doxycycline in the treatment of severe mycoplasma pneumoniae pneumonia (MPP) in children. Methods: From January 2024 to October 2024, 200 children with severe MPP in our hospital were selected and divided into groups according to random number table method. 100 children in the high-dose group were treated with 2 mg·(kg·times)-1 doxycycline twice a day, and the low-dose group was treated with 2 mg·(kg·times)-1 once a day. The maximum single dose of the two groups was less than 100 mg. The therapeutic effect of continuous treatment for 72 h in the two groups was observed, the improvement time of symptoms and the length of hospital stay were compared, and the changes of serum lactate dehydrogenase (LDH) level, C-reactive protein (CRP) level and procalcitonin (PCT) level before and after 72 h of treatment in the two groups were compared, and the occurrence of adverse reactions in the two groups were analyzed. Results: The total effective rate of high dose group was higher than that of low dose group (P<0.05). There was no significant difference in fever resolution time between the two groups (P>0.05), but the time of cough disappearance, rales disappearance and hospital stay in the high-dose group were shorter than those in the lowdose group (P<0.05). Serum LDH, CRP and PCT levels in 2 groups after 72 h treatment were significantly lower than those before treatment, and high dose group was lower than low dose group (P<0.05). The overall incidence of adverse reactions in low dose group was significantly lower than that in high dose group (P<0.05). Conclusion: Doxycycline 2 mg·(kg·times)-1 twice a day is more effective than doxycycline once a day in the treatment of severe MPP in children. High dose of doxycycline is more helpful to early improvement of symptoms and laboratory indicators, but may lead to higher risk of adverse reactions.