Immediately after the outbreak of World War I, Empress Alexandra Feodorovna ordered to open three infirmaries at Tsarskoe Selo to treat the wounded: at the Tsarskoe Selo Home for Disabled Soldiers, at the Tsarskoe Selo Red Cross Community and at the Palace Hospital. Private individuals followed in her footsteps and began to open small infirmaries in their homes.

Wishing to take a personal part in helping the wounded, Empress Alexandra Feodorovna, along with her daughters Olga and Tatiana, took nursing lessons under the guidance of a doctor at the Palace Hospital, Princess Vera Ignatievna Gedroits, and then assisted her during operations as surgical nurses.

The ever-increasing flow of wounded soon led to a greater demand in the number of infirmaries in the Tsarskoe Selo district. For these purposes, it was decided to use apartments in the Catherine Palace. The infirmary occupied the rooms of Grand Duke Pavel Alexandrovich and his children, as well as adjacent rooms overlooking the Catherine Park and the rooms of Princess Yurievskaya on the ground floor of the Zubov wing.

The infirmary for wounded soldiers in the Great Palace of Tsarskoe Selo opened on October 30, 1914 and could fit 40 beds for officers. The infirmary was consecrated on November 6, 1914 in the presence of Empress Alexandra Feodorovna and Grand Duchesses Olga Nikolaevna and Tatiana Nikolaevna. Colonel Alexander Alexandrovich Gebel was appointed the head of the infirmary at the Great Palace of Tsarskoe Selo. Vladimir Nikolaevich Derevenko, the honorary surgeon of the heir to the throne, was invited to work as senior doctor. Yulia Alekseyevna Lyubushina, a sister of mercy from the Petrograd Community of St. Eugenia, was appointed the senior nurse.

The money for the maintenance and equipment of the infirmary came from the Cabinet of His Imperial Majesty of the Ministry of the Imperial Court. Nurses were paid 15 rubles, while senior doctors received 350 rubles. In the first month after the opening, Empress Alexandra Feodorovna visited the new infirmary almost every day. Later, Alexandra Feodorovna focused her attention on working in the infirmary at the Palace Hospital and visited the Great Palace infirmary no more than once or twice a month.