Behavioral assessment of rodents is critical for investigation of brain function in health and disease. In vivo neurophysiological recordings are powerful tools to mechanistically dissect neural pathways that underlie behavioral changes, and serve as markers for dynamics, efficacy and safety of potential therapeutic approaches. However, most in vivo recording systems require tethers or telemetry receivers, limiting their compatibility with some behavioral tests. Here, we developed an open-source standalone electrophysiology recording system for rodents (OSERR). It is a tether-free, standalone recording device with two channels, a reference and a ground, that acquires, amplifies, filters and stores data all in itself. Thus, it does not require any cable or receiver. It is also compact and light-weight, and compatible with juvenile mice, as well as multiple recording modalities and standard electrode implantation methods. In addition, we provide the complete design of hardware, and software for operation. As an example, we demonstrated that this standalone system, when configured with a bandwidth of 1–120 Hz and gain of 1000, successfully collected EEG signals during induced seizure, extended recording, anesthesia, and social interactions in mice. The design of this system is practical, economical, and freely available. Thus, this system could enable recording of brain activity during diverse behavioral assays in a variety of arenas and settings, and allow simultaneous recordings from multiple subjects to examine social behaviors. Importantly, with the open-source documentation, researchers could customize the design of the system to their specific needs.