Asthma has been associated with a sharp increase in the global prevalence, morbidity, mortality, and economic burden over the past several years. This paper presents a vitals monitoring system-on-chip (SoC) that measures the heart rate (HR), and its variability (HRV), blood oxygen saturation (SpO2), and respiratory rate (RR) from a Photoplethysmography signal (PPG). The proposed SoC integrates a direct current-to-digital analog front end for PPG signal acquisition, a vitals extraction processor, and a time-multiplexed LED driver for red and IR LEDs. The PPG readout employs a second-order, continuous-time, delta-sigma analog to digital converter (ΔΣ-ADC) with a 0.1% duty-cycled operation to reduce power consumption while achieving a 110dB dynamic range. The SoC is implemented in a 180nm CMOS process with an active area of 4.5mm2. The functionality of the proposed SoC is verified on patients’ recordings from Beth Israel Deaconess Medical Center (BIDMC). The proposed SoC achieves high accuracy measurements with a maximum absolute error percentage of <2% for all vitals while consuming 385µW.