This study was aimed to investigate the effects of different fresh gas (oxygen + air) flow rates and different anesthetics on airway temperature and humidity when using the same anesthesia machine in patients undergoing general anesthesia. In this prospective, observational study, 240 patients with American Society of Anesthesiologists (ASA) I-II between the age of 18-65 years to be operated under general anesthesia were enrolled and divided into two groups according to the fresh gas flow rate (3-6 L/min). Each of the two main groups was further divided into three subgroups according to the administered anesthetic gases and drugs. The resulting six groups were further divided into two subgroups according to whether the heat and humidity exchanger filter (HME) was attached to the breathing circuit, and the study was carried out on a total of 12 groups. The temperature and humidity of the inspired air were recorded every 10 minutes using an electronic thermo-hygrometer. The inspired temperature and humidity were greater in patients ventilated at 3 L/min compared to the 6 L/min group and in HME (+) patients compared to HME (-), regardless of the type of anesthetics. HME application makes the air more physiological for the respiratory tract by increasing the temperature and humidity of the air regardless of the anesthetic agent. This study was approved by Ethics Committee Review of Selcuk University Faculty of Medicine (No. 2017/261) in September 2017, and was registered in the Clinical Trial Registry (identifier No. NCT04204746) on December 19, 2019.