According to the existing scenarios of interplanetary missions, the Moon is considered as an intermediate base on the way to deep space. In order to prepare for landing and work on the Moon, it is important to study the applicability of countermeasures in such missions. The paper presents the results of a pilot study performed during a short-term spaceflight (12 days). A new experience of using countermeasure impacts of lower body negative pressure (LBNP) at the early stages of adaptation to microgravity conditions has been gained. To assess the effectiveness of LBNP and changes in human physical performance after the spaceflight, we conducted tests on a treadmill, a bicycle ergometer, and testing with model tasks of on-planetary activity "express test". Regulatory mechanisms of the cardiovascular system proved to be quite effective when creating decompression up to -20 mm Hg, which is less than in preparation for returning to Earth. In the treadmill test, a lower speed was achieved after the spaceflight than before (13 km/h and 15 km/h, respectively) and cardiovascular system response to the change in load was slower. At the same time changes in such physiological parameters as oxygen consumption, respiratory rate and pulmonary ventilation were minimal. In the bicycle ergometer test, peak heart rate values were higher after the spaceflight than before, the physiological value of the standard exercise increased. «Express test» showed the positive dynamics from the first day to the third after returning to Earth: the performance of a dual task, the task of controlling the movement of the non-leading hand, and getting up from the supine position improved. Thus, assessment of the state of gravity-dependent physiological systems after short-term flight indicates the decrease of functional reserves of the organism and the necessity to develop appropriate countermeasures. The study was one of the first steps in the development of new medical control operations at the stage of paradigm shift from orbital flights to deep space exploration.