Abstract Objective. Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at medical proton sources. Yet, LPAs pose challenges regarding precise and accurate dosimetry due to the high pulse dose rates, but also due to the sources’ lower spectral stability and pulsed operation mode. For in vivo models, further challenges arise from the necessary small field dosimetry for volumetric dose distributions. For these novel source parameters and intended applications, a dosimetric standard needs to be established. Approach. In this work, we present a dosimetry and beam monitoring framework for in vivo irradiations of small target volumes with LPA protons, solving aforementioned challenges. The volumetric dose distribution in a sample (mean dose value and lateral/depth dose inhomogeneity) is provided by combining two independent dose measurements using radiochromic films (dose rate-independent) and ionization chambers (dose rate-dependent), respectively. The unique feature of the dosimetric setup is beam monitoring with a transmission time-of-flight spectrometer to quantify spectral fluctuations of the irradiating proton pulses. The resulting changes in the depth dose profile during irradiation of an in vivo sample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement. Main results. A first successful small animal pilot study using an LPA proton source serves as a testcase for the presented dosimetry approach and proves its performance in a realistic setting. Significance. With several facilities worldwide either setting up or already using LPA infrastructure for radiobiological studies with protons, the importance of LPA-adapted dosimetric frameworks as presented in this work is clearly underlined.