Current oxygen delivery modes lack monitoring and can be cumbersome for patients with chronic respiratory diseases. Integrating a pulse oximeter and nasal oxygen cannulas into eyeglasses would reduce the burden of current solutions. An ear pulse oximeter (OxyFrame) was evaluated on 16 healthy volunteers and 20 hypoxemic patients with chronic respiratory diseases undergoing a prespecified protocol simulating daily activities. Correlation, error, and accuracy root mean square error (ARMS) were calculated to compare SpO2 measured by OxyFrame, a standard pulse oximeter (MASIMO), and arterial blood gas analysis (aBGA). SpO2 measured by OxyFrame and MASIMO correlated strongly in volunteers, with low error and high accuracy (r = 0.85, error = 0.2 ± 2.9%, ARMS = 2.88%). Performances were similar in patients (r = 0.87, error 0 ± 2.5%, ARMS = 2.49% compared with MASIMO; and r = 0.93, error = 0.4 ± 1.9%, ARMS = 1.94% compared with aBGA). However, the percentage of rejected measurements was high (volunteers 77.2%, patients 46.9%). The OxyFrame cavum conchae pulse oximeter was successfully evaluated, and demonstrated accurate SpO2 measurements, compliant with ISO 80601-2-61:2017. Several reasons for the high rejection rate were identified, and potential solutions were proposed, which might be valuable for optimization of the sensor hardware.