This paper presents a miniaturized EPR spectrometer based on a single-chip transceiver. Utilizing a novel on-chip self-interference cancellation circuit, the electromagnetic coupling from the transmitter (TX) to the receiver (RX) is minimized, allowing simultaneous achievement of large TX output power and low RX noise figure (NF). In the measurement, the RX achieves a NF of 3.1 dB/6.3 dB at 10 MHz/50 kHz baseband frequencies, when the TX and cancellation circuits are turned off. The measured flicker noise corner is 60 kHz, more than $10\times $ lower than the prior work. Moreover, for the first time, the operation of the RX and cancellation circuit is demonstrated when a co-integrated TX is operating at the same time and frequency, while producing >20 dBm output power. When the TX and cancellation circuits are turned on, at −10 dBm interference power, the measured NF is 6.8 dB/11.1 dB at 10 MHz/50 kHz baseband frequencies. This is lower by 5.6 dB/9.6 dB at 10 MHz/50 kHz baseband frequencies, compared to the NF with the cancellation circuit off at the same interference power. The transceiver chip is implemented in IBM $0.13~\mu \text {m}$ BiCMOS process and consumes a power of 2 W. Utilizing this transceiver, an electron paramagnetic resonance (EPR) spectrometer is built and tested. It is observed, through measurement, that the interference cancellation circuit increases the signal-to-noise ratio (SNR) of the EPR signal by 7 dB at −10 dBm interference power. Compared to prior work, the reported EPR spectrometer improves the sensitivity of the system by 25 dB.